Fight Aging!

A good deal of the art of tissue engineering lies in the complexities of the scaffold used to support and guide cell growth. Here, Nanowerk takes a look at ongoing research into the technology necessary for a safe and reliable replacement parts industry for humans: "At the core of tissue engineering is the construction of three-dimensional scaffolds out of biomaterials to provide mechanical support and guide cell growth into new tissues or organs. Biomaterials can be variously permanent or biodegradable, naturally occurring or synthetic, but inevitably need to be biocompatible. Using nanotechnology, biomaterial scaffolds can be manipulated at atomic, molecular, and macromolecular levels. ... For bone tissue engineering, a special subset of osteoinductive, osteoconductive, integrative and mechanically compatible materials are required. Such materials need to provide cell anchorage sites, mechanical stability, structural guidance and an in vivo milieu. Moreover, they need to provide an interface able to respond to local physiological and biological changes and to remodel the extracellular matrix (ECM) in order to integrate with the surrounding native tissue. Scientists in Singapore have developed a new nanoscale biocomposite that brings researchers one step closer to mimicking the architecture of the ECM."

Link: http://www.nanowerk.com/spotlight/spotid=1374.php

From Fortune, a short look at the near future of calorie restriction mimetic and related drugs - how far can longevity be taken by the manipulation of metabolism at its critical points? "Many experts believe that drugs are on the horizon which could extend average life span by perhaps five to ten years. That may seem unimpressive. But their boost to life expectancy would 'far exceed' that from totally eliminating cancer, says S. Jay Olshansky ... That's because the risk of many deadly diseases skyrockets as we age, so even if one were vanquished, the others would soon get us, limiting the gain in average life span. In contrast, an anti-aging drug, almost by definition, would retard all major diseases of aging at once. ... In 2005 the Rand Corp. consulted medical experts on this question and reported that they believe there's a 50 percent chance that anti-aging drugs will be available within 20 years. Some researchers on aging, such as Harvard's David Sinclair, believe that medicines like those will come along much sooner - perhaps within a decade." This is, however, the slow path for any greater extension of healthy life span. We can do much better, given a change in focus and greater funding for repair over metabolic manipulation.

Link: http://money.cnn.com/2007/01/30/magazines/fortune/anti-aging_drugs.fortune/

I felt I should share this item with you; it is illustrative of the attitudes of a certain set of people who stand in opposition to healthy life extension, and illustrative of a certain sickness that has crept into the minds of men in modern times. It is a petition upon an open access UK government website - there is something of a trend in that country towards using the tools of the web in this sort of manner; time will tell if anything meaningful comes of it. In any case, here is the view of one person as a concisely condensed compilation of the views of many more:

We the undersigned petition the Prime Minister to Ban all scientific research aimed solely at increasing longevity past 70 years.

...

A number of biotechnology companies (which cannot be named here) are trying to allow rich people to extend their lifespans to over 100 years using pharmaceuticals. Unfortunately, this could take money from the poor and give it to the rich (in their long pensions) by increasing everyone else's pension contributions, and housing and healthcare costs. All health research directed towards extending longevity beyond 70 years should be banned to save our pension system and NHS from collapse and to give room for the wonders of the next generation.

Impressively condensed, no? One scarely knows where to start.

As I've discussed in the past, many people play host to a fear of change so great they would rather suffer and die than work to improve the world. Worship of "the system" is symptomatic of this internal rot - there is no system of governance and regulation so bad, so horrible, so destructive that it has no slavish defenders. Imagine - a set of laws to take money from one set of people and give it to another has grown such an ossified cult that there are millions who cannot imagine a world even slightly different, and who would go to their deaths rather than think about changing matters for the better.

Another of my numerous soapboxes, well illustrated in the quote above, is the effect of economic ignorance upon the world.

Life is unfair, make no mistake. People are unequal in opportunity, capacity and the hand they were dealt at birth. To think that this truth can be removed in any way, shape or form is to betray a profound ignorance of economics and the human condition. You cannot make life better at the bottom by tearing down the top; the top is where progress happens, progress that lifts the quality of life for everyone. Punishing success in order to reward failure has predictable results - more failure and less success. The wealthy of 1950 were far worse off than the poor of today precisely because progress brings economic rewards to the successful.

Arguments based on inequality are, at root, made from a misunderstanding - willful or otherwise - of the way in which wealth, medicine and technology are best created. Rapid progress for all requires a free market, strong rule of law and property rights. Such a culture necessarily has a power law distribution of ownership and success. There's a reason the US has led the world in technology, for all that it's going to the dogs nowadays - it's the flip side of the reason that communism, socialism and the politics of envy lead to poverty and suffering.

Creating "equality" by taking from the successful ruins the creation of wealth - very much a non-zero sum game - for all. It takes away the vital incentives and rewards for success. At the end of the process, as demonstrated by all that transpired in the Soviet Union, you are left with the same old inequalities, but now taking place amongst ruins, starvation and disease.

Not to mention the tragedy of the commons that is socialized medicine - a surefire way to turn plenty into poverty by disconnecting usage from responsibility and cost, transforming the non-zero-sum game of economic growth and transaction into a zero-sum game of selfishness and destruction. Commons have a way of turning people perfectly capable of responsibility into helpless, childlike losers who will claw the eyes from anyone they think is doing better, but who will perform not one iota of work to improve the situation for all.

The world of government-enforced commons is a twisted mirrorland, in which more years of healthy life, a greater ability to work, a greater call for products and production are made into a black destruction - rather than the very lifeblood of opportunity, economic growth and happiness they are in a free economy.

Do we really live in a world in which our deaths - on time, to a schedule laid down by government employees - are required to fuel "the system?" Or do we live in a world in which we strive to produce more and better life, and in which rules are made to serve the interests of people rather than vice versa? The answer to that question is up to us.

Technorati tags: economics, life extension

Cancer cells are different - and biotechnology in the labs can target those differences. As research continues, and the capabilities of the biotechnology toolkit advance, we should expect ever more potential target differences to emerge. Here is one more, from the Washington Post: "Most of the growth of cancer cells is governed by so-called 'weak' messenger RNAs, which tell the cell what proteins to make. Wagner believes that by exploiting this weakness in cancer cells, scientists can stop these cells from growing. This is done by finding small molecules that can attach themselves to the surface of cancer cells and block the messenger RNAs from communicating with the cells. ... Wagner's team discovered a small molecule that inhibits the growth of cancer cells but has no effect on the proteins necessary for the functioning of normal cells. The molecule, called 4EGI-1, effectively silences genes that have links to cancer ... New technology is going to give us molecules that are designed to fit the shape of proteins we want to disrupt. Then, if you think about what you want to disrupt, well, there's a whole new pharmacology out there." Early days yet, but it's amazing just how much broader the future horizons of medicine are becoming.

Link: http://www.washingtonpost.com/wp-dyn/content/article/2007/01/25/AR2007012500879.html

A brief release from EurekAlert! is illustrative of the spread of examining changes of gene expression with aging. That knowledge should provide a starting point for further research to understand why tissues act differently with age, as well as the root causes of these changes. In this case, the tissue in question is skin: researchers aim "to identify how genetic expression in the skin changes with ageing and how it can affect the comparative healing and scarring rates of older and younger people. Findings from the study will go towards achieving our ultimate goal of reducing the disfigurement associated with burn injury. We also hope to gain important knowledge for the development of tailored burns treatments based on an individual's unique combination of genes." Sooner or later, tracking down the whys and wherefores for all the biochemical changes that make up age will produce sufficent knowledge and tools to do something about age-related degeneration and death.

Link: http://www.eurekalert.org/pub_releases/2007-01/ra-sam012907.php

Study and careful inference is a bedrock of scientific progress - and so one has to be careful with the concepts of correlation and causation whenever reading about the latest science. We humans are built to see causation everywhere, to pick out patterns from nothing with our hyperactive pattern detectors - even when it doesn't in fact exist. The culture and methods of science exist to rein in the excess, to pick out the flotsam of right answers from the vast sea of wrong answers.

The scientific method is the cure for problems caused by magical thinking, such as a lack of progress towards better lives, and all the limitations - dramatic or trivial - that stem from an incorrect understanding of the way in which the world works. To make progress happen, you must tackle complex systems in a methodical way: propose, explore, test, verify, record, repeat. But that requires more work than merely guessing, and so there will always be some market for those willing to take the "shortcut" to the wrong answer. When the wrong answer doesn't have clear, obvious and rapid bad consequences attatched to it, magical thinking will prosper. Such is the downside of human enonomic preferences - there is always a market for "incorrect" when "incorrect" is sold more cheaply than "correct."

But back to correlation; I bumped into a rather good post on the topic that exercises a number of the same frustrations I note when reading about science in the popular press. No-one is as careful as they should be, sadly, and so much of what passes for information is in fact misinformation. Correlation does not imply causation, and noted correlation is often not in fact correlation - and much of the supposed causation isn't much more than wishful thinking either. In any case, the good post is at Good Math, Bad Math:

Correlation is actually a remarkably simple concept, which makes it all the more frustrating to see the nonsense constantly spewed in talking about it. Correlation is a linear relationship between two random variables.

...

One thing you'll constantly hear in discussions is "correlation does not imply causation". Causation isn't really a mathematical notion - and that's the root of that confusion. Correlation means that as one value changes, another variable changes in the same way. Causation means that when one value changes, it causes the other to change. There is a very big difference between causation and correlation. To give a rather commonly abused example: the majority of children with autism are diagnosed between the ages of 18 months and three years old. That's also the same period of time when children receive a large number of immunizations. So people see the correlation between receiving immunizations and the diagnosis of autism, and assume that that means that the immunizations cause autism. But in fact, there is no causal linkage. The causal factor in both cases is age: there is a particular age when a child's intellectual development reaches a stage when autism becomes obvious; and there is a particular age when certain vaccinations are traditionally given. It just happens that they're roughly the same age.

...

To show causation, you need to show a mechanism for the cause, and demonstrate that mechanism experimentally. So when someone shows you a correlation, what you should do is look for a plausible causal mechanism, and see if there's any experimental data to support it. Without a demonstrable causal mechanism, you can't be sure that there's a causal relationship - it's just a correlation.

How do you know that reported science is relevant and useful to healthy life extension and the advance of medicine? It certainly shouldn't be because someone is telling you as much, directly and outright. Always look a little deeper; take a little time to explore the underlying facts and ideas in any new scientific news for yourself to see if they make sense.

Technorati tags: causation, correlation

From EurekAlert!: "The number of individuals with Parkinson's disease in 15 of the world's largest nations will double over the next generation ... While the number of individuals with the disease will nearly double in the United States to 610,000, the greatest growth will occur in developing countries in Asia. By 2030, an estimated 5 million people in China will have the disease." This, it should be taken as read, is a picture of a future in which medical science does not advance as rapidly as it might - in which the relentless advance of biotechnology and the engines of commercialization fail to churn out effective therapies that rapidly decrease in cost while increasing in availability and effectiveness. Parkinson's disease is just one of many failure modes of age-damaged cells and biochemistry in the nervous system and brain; if we are to do our very best to save as many lives as possible from age-related suffering, frailty and death, we must work hard indeed to support the best and most effective research and remove roadblocks to the development of therapies.

Link: http://www.eurekalert.org/pub_releases/2007-01/uorm-wpc012907.php

Biosingularity should be in your aggregated RSS feed if it isn't already. Here, Attila Chordash of Pimm conducts another of his interviews with life scientists and advocates who support healthy life extension: "What really surprises me is that one has to make an argument about [life extension]. As a medical doctor I am trained to save human lives, regardless what age you are as long as you are committed to living. ... The point is not live forever, the purpose of all medical science is to give people chance to live from things they die if they want to continue living, including those that kill you because your body ages. I am going to be blunt and say that it is nonsense that we have to make an argument for life! ... Treating or controlling indefinitely all chronic deadly human diseases should be achievable within the next 25-30 years ... I anticipate continuous body regeneration soon after that within the next 40 years. ... Once we achieve biosingularity, a point when we can completely reprogram and regenerate and design from scratch novel biological systems, we should have achieved not only indefinite life span but also began reversal of aging. I anticipate around mid of this century people will look back to now, as we have do for those who lived hundred of years ago, and feel sorry how little control we had."

Link: http://pimm.wordpress.com/2007/01/29/biosingularitys-derya-unutmaz-a-t-cell-expert-on-life-extension/

As one of the go-to people when the media wants to talk about the practice of calorie restriction (CR) for health and longevity, Methuselah Foundation volunteer and blogger April Smith gets her fair share of undeserved snark, vitriol and general rudeness. She recently set up a little essay contest between friends, bloggers and calorie restriction practitioners on the topic of "Why are people so hateful about CR?" It's been a couple of weeks, and now you'll find the winning entries over at April's blog:

I remember what it was like to weigh 25 more pounds than I weigh now and to be unhappy, heaviness causing the sadness as much as the other caused the other, and it seems impossibly sad to watch people your own age go down a totally avoidable path if they just would get straight in their own heads.

Why do I think people are so virulently against CR? In a country where the average American woman is a size 14, even adjusted for vanity sizing, it's an easy target. While CR could easily put on a pious front, it is, these days, the fat that reserve that for themselves.

Watch a taped performance from 25 years ago, one with frequent shots of audience members enjoying the actors. Watch one today. The face of America is changing. It has a double chin and the upper body of a long-former linebacker. And if you're not with the expanding beltline, you're against it.

Calorie restriction is not about weight loss - and yet the elephants in the room aren't going to leave you alone even if you're marching to a different tune. CR is a matter of looking at the compelling decades of scientific backing for eating fewer calories with optimal nutrition in search of a healthy, longer life. But you get thin as a side effect, and those who are engaged in fighting their own battles over fat, size, and a wealth of related issues near and dear to the apes we are at heart will drag you right on in - if you let them.

But CR has nothing to do with any of that. It's about proven health benefits; the only technique you can practice right now to improve healthy longevity that has a meaningful weight of science backing it up.

Technorati tags: calorie restriction

Medgadget notes work on delivering vaccines for Alzheimer's via the skin: "The Alzheimer's vaccine works by triggering the immune system to recognize Ab -- a protein that abnormally builds up in the brains of Alzheimer's patients -- as a foreign invader and attack it. Previous research on an injectable Alzheimer's vaccine proven safe and effective in an animal model was suspended indefinitely when the initial clinical trial caused brain inflammation and death in a small percentage of patients. These serious side effects were secondary to an autoimmune reaction, which occurred when immune cells aggressively attacked the body's own proteins produced by the vaccine. ... transdermal immunization with Ab does not appear to trigger specific toxicities associated with past immunization strategies. Specialized immune cells prevalent in the skin, called Langerhans, may direct the body's reaction to the vaccine toward a response that is beneficial instead of overly aggressive and ultimately harmful."

Link: http://www.medgadget.com/archives/2007/01/antialzheimers.html

Whenever discussion of healthy life extension reaches a certain threshold in the media, or somehow encompasses the viewpoints of a wide range of people, I am reminded that we advocates still have a long way to go in propagating and reinforcing the most basic ideas. We have made a great deal of progress in the past few years, but it's still that case that the vast majority of people have yet to internalize:

• That healthy life extension means being healthy and youthful for longer, not old, suffering and frail for longer
• That significant progress in lengthening the healthy human life span is plausible within the next few decades, with the right level of support
• That there are easy ways for average, everyday folk to help make this happen
• That much of the common wisdom on aging and death stems from millennia of rationalizing the inevitable, but is no longer relevant in an era in which we can do something about aging

I am reminded of this today by yet another commentary on "How to Live Forever or Die Trying" - a book on the culture and science of radical life extension by a fellow who is getting real value from the marketing and promotion spend, it would seem. It is interesting that many of the reviews are basically apologies for death and suffering, and a denial that any change for the better - any attempt to save the tens of millions of lives lost each year, in other words - should be undertaken. Like this one:

In a pacy narrative of the mind, where Descartes meets Wittgenstein and Aquinas rubs shoulders with Swedenborg, Appleyard is steering us in this age of encroaching death denial towards that inevitable question: am I a “deathist” or an “immortalist”? Do I live by accepting death, or by rejecting it? Appleyard argues in conclusion: “All our stories, myths and meanings are constructed on death, on a knowable, shared progress from the cradle to the grave . . . If we live for ever, not only will our particular loves die, love itself will die of thirst, a thirst for death.” He is, of course, profoundly right, but accompanying him on his riveting helter-skelter of a literary journey not only confirms but deepens the humane wisdom of that positive conviction.

There's nothing wrong with choosing death and oblivion - a world founded on individual choice and respect for those choices would be a better place to live in that the one we presently have - but all too many people are doing so in ignorance of the possibilities for more and better years of life in the near future. We advocates need to work harder at pounding on the basics, broading the reach of education and awareness, and making the simple points clearly understood. Life is good, so why not more of it?

Technorati tags: advocacy, book, life extension, review

Here, Anne C. comments on an issue I have brought up at times in the past: the healthy life extension advocates of 30 years ago were absolutely wrong in their focus and predictions. They existed in the old school world of producing desired changes in aging through the brute force application of simple chemicals, with meaningful success promised in the 1990s - an impossible dream, given the science of the time. Yet today advocates say essentially the same things, and with similar timescales for predictions of progress and success. Why are we right while the past generation was so wrong? The answer to this question is clear: it is the capabilities and speed of advance of modern biotechnology, the same reason that cancer will be successfully treated and managed in the late 2010s rather than the late 1980s. We must be wary, however, of falling into the same trap as those past advocates - of seeking an answer, any answer that promises success soon, at the expense of the most plausibly correct answer. We're not here to promise rescue from aging - leave that to the "anti-aging" charlatans. We're here to make meaningful, rapid progress towards the technology that will one day rescue us from aging. We need to be realistic about whether that is possible within our lifetimes - but the goal is worthy whether or not that is the case.

Link: http://rationallongevity.blogspot.com/2007/01/avoiding-past-mistakes-in-longevity.html

At Newswise, you'll find more science backing up common sense practices for long term health: calorie restriction and exercise. "Dieting alone is equally effective at reducing weight and fat as a combination of diet and exercise - as long as the calories consumed and burned equal out. The research also indicates that the addition of exercise to a weight-loss regimen does not change body composition and abdominal fat distribution, debunking the idea that specific exercises can reduce fat in targeted areas ... It's all about the calories. So long as the energy deficit is the same, body weight, fat weight, and abdominal fat will all decrease in the same way." But exercise and calorie restriction do not have the same results on long-term health, even through they both reduce the excess fat that is a risk for many age-related conditions. "Exercise improved aerobic fitness, which has other important cardiovascular and metabolic implications." And calorie restriction has benefits in terms of resisting age-related disease that exercise does not. "For overall health, an appropriate program of diet and exercise is still the best." You're going to have wait out the arrival of real, working rejuvenation medicine - so why shorten your healthy life through neglect of the basics?

Link: http://www.newswise.com/articles/view/526694/

You should pay attention to the basic building blocks of biotechnology - you'll be far better placed to determine hype from important breakthrough. With that in mind, have a look at this NYAS overview: "novel drugs made from short nucleic acid segments, or oligonucleotides, can target DNA and RNA to inactivate genes involved in causing disease. ... Some of these oligonucleotides have the ability to stimulate the immune system [and] could be employed against cancer, viral diseases, or as immune system boosters for vaccines or chemotherapeutics. Perhaps the most important discovery to affect the development of oligonucleotide therapeutics has been that of RNA interference (RNAi), a mechanism by which RNA inhibits gene expression. ... small 21- to 23-nucleotide double-stranded RNAs called short interfering RNAs (siRNA) [are] capable of knocking down specific gene expression to a few percent of its original level. ... Therapeutics based on siRNA are also being developed as treatments for age-related macular degeneration, respiratory syncytial virus infection, hepatitis C, and HIV infections." Perhaps most interestingly, given the prominent role of HCMV in the age-related decay of our immune systems, "RNAs known as ribozymes can inactivate viruses such as human cytomegalovirus (HCMV)."

Link: http://www.nyas.org/ebriefreps/main.asp?intSubsectionID=4258

Scheduled for the evening of February 3rd, Channel 4 in the UK will be airing Christopher Sykes' documentary on biomedical gerontologist Aubrey de Grey, the Strategies for Engineered Negligible Senescence (SENS) and the scientific goal of radical life extension. Aging is damage, damage can be repaired, and SENS is a first, coherent stab at outlining exactly - to the best of our knowledge today - how the biotechnology and research communities could accomplish this goal. From the Channel 4 website:

Computer scientist turned biologist Dr Aubrey de Grey is on a mission to end 'the scandal of death. Award-winning filmmaker Christopher Sykes goes on the road with de Grey to find out whether old age and death could soon be a thing of the past.

I believe it should be possible to watch this online on the 3rd via the simulcast section of the website, though I haven't given this functionality a road test myself.

From Christopher Sykes' website:

Investigating the revolutionary life-extension ideas of AUBREY de GREY, immortalist and biogerontologist extraordinary, architect of the SENS programme to defeat old age and conquer death within his own lifetime.

Here are the Radio Times details:

Award-winning director Christopher Sykes follows computer scientist turned renowned biologist Dr Aubrey de Grey on the road as he investigates the possibilites of immortality. Hailed as a genius by some experts and publicly denounced by other scientists, de Grey expands on his theory of immortal life by identifying the 'Seven Deadly Things' that cause ageing and proposes solutions for them all. Will this lead to indefinite life extension in the future and is it something we really want?

As I've said a number of times in the past, the word "immortality" seems to be acquiring a common meaning of "greatly extending healthy life span," at least in the media. The shorthand of journalism, to convey much in title and snippet by the use of few words - or less charitably, to make every word pull its weight in the act of attracting fleeting attention, any attention, in a Darwinian struggle for survival - but it would have been nice had the community settled on a word less loaded with pre-existing meaning.

Technorati tags: documentary, media, SENS

Via Fox News, an article illustrative of present levels of investment in the stem cell banking industry: "Sir Richard Branson will launch his most controversial business to date as he moves into stem-cell storage and the biotech sector ... The Virgin-branded company will be launched next Thursday and is expected to offer parents the chance to put the umbilical blood of their newborn children into cold storage. Scientists believe that future advances in medical technology will use stem cells to cure diseases such as Alzheimer's and cancer. ... Public cord storage is becoming more common, particularly in the U.S., but there is also a growing private industry taking advantage of the promise of these cures." It's a form of insurance in an uncertain world; as I've pointed out previously, it's an open question as to how rapidly the advance of biotechnology will render stored cells moot. But if the cost becomes low enough, why not bank the cells anyway? The sure way to lower cost and better service is more investment and competition between service providers.

Link: http://www.foxnews.com/printer_friendly_story/0,3566,247038,00.html

Here, via the Guardian is another commentary on "How to Live Forever or Die Trying" to accompany the reviews noted in past days at Fight Aging! "Will immortality even devalue love, and work, and other things we find meaningful in this earthly life? If there is a limitation to Appleyard's field of reference, it is that he doesn't acknowledge the fact that such questions have been worried at, and dramatised, for a long time now by science-fiction writers. The colourful, scholarly, serially monogamous existences of very long-lived humans in the novels of Iain M Banks or Peter F Hamilton - the writers of 'space operas' who combine cosmological speculation with dense social imagination - certainly don't seem bored to death. And if such existences can be imagined, they may not turn out to be quite so alien to us as the pessimists suppose. Appleyard rightly notes that the initial advent of medical immortality will have huge and perhaps dangerous social consequences, but disruptive technologies always do: the question is whether the benefit - freedom from death, which is the condition of all other possible freedoms - can really be passed up."

Link: http://books.guardian.co.uk/reviews/scienceandnature/0,,1999578,00.html

A BBC interview with biomedical gerontologist Aubrey de Grey - from way back in the dark ages of late 2004 - is once more making the rounds of the vast interconnected conversation of the blogosphere, social news networks and attention aggregators. This whole distributed process by which older content fountains up once more for a brief period is quite fascinating, as I noted the last time it happened for this article:

In the past few years the traditional print world focus on new, fresh content has come to overwhelmingly dominate the online spaces, thanks to the popularity of sequential publishing models; RSS, blogs, aggregation and default searches orded by date. That said, popular link sites or pseudo-news sites (Slashot, Digg, Metafilter, so forth) can cheerfully buck this trend and point out older content that might be fresh for a given audience. That audience will then respond by reading, reprinting, discussing and linking to the older content for a while.

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The Digg audience found this compelling, and I don't blame them; it is pretty damn compelling. As I pointed out yesterday, while the concepts of radical life extension are old hat for transhumanists and other healthy life extension advocates, they remains uncharted territory and new news for the vast majority of people.

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People find radical life extension compelling, and rightly so. The mini-wave of interest in this BBC interview was accompanied by a mini-wave of donations and inquiries to the MPrize for anti-aging research and Methuselah Foundation - that is a hopeful sign.

This time too - the rate at which new members have joined the The Three Hundred and new donations in support of rejuvenation research arrived at the Methuselah Foundation has risen in the past few weeks. I'm always pleased to see more people taking the time to learn about the prospects for healthy life extension in our lifetimes, achieved through scientific research and the new tools of biotechnology.

The vigor of this information dredge and recirculation mechanism seems - to my eye at least - to be a better measure of interest in and effectiveness of communication strategies than a response on initial publication. The question presently in my mind is why this particular BBC article returns again and again. Why not any of the many other interesting, well-written and informative interviews, profiles and articles on de Grey and his Strategies for Engineered Negligible Senescence (SENS) that are presently available online? What is it about this article that makes it so compelling, so effective at education and raising awareness? There is something to be learned here for those of us who would like to see healthy life extension science discussed and supported far more widely than it is at present.

Technorati tags: advocacy, life extension, SENS

Sad to say, but there exist any number of people willing to stand up and tell us how wonderful and necessary suffering and death by aging are to the world. They're all full of it, terrified of change or living - and how dare they stand up and speak for those who are aged now. Read this blog entry by a 93-year old, and consider what the Kasses and Fukuyamas of the world would like to do to all of us - condemn us all to age, suffer and die to their schedule, rather than the years we strive to make for ourselves. "At this age, I must say that I do delight in people's amazement when I tell them how old I am. But under all this is the knowledge that I am the oldest male on either side of my family, maternal or paternal, and I know I must go fairly soon. I just don't like the idea. ... There are many reasons. For too long I have behaved as if I could postpone going indefinitely, and thus have so many things that I must do first. I don't want my successors to find out how much I could have done that isn't done, not by a long shot. There are numerous notes and letters I must write. There are places I've wanted to travel, but never had the chance. Actually, each of you can, if you think yourself into my age, fill out the list. At least you can try to understand why I say that I hate to go." We strive for a world in which no-one has to experience this - in which there is no daily toll, no 100,000 deaths by each new sunset.

Link: http://dontoearth.blogspot.com/2007/01/it-bothers-me-that-i-have-to-go.html

Chronic inflammation appears to raise risk across the board for the diseases of aging - it is a source of damage to the cellular machinery that is you. Here, ScienceDaily looks at an advance in understanding why inflammation leads to a greater risk of cancer: "Cellular defense is a rapid process compared to cellular development [but] safeguarding against threats and building structures have certain steps in common and require similar types of workers, or molecules. ... the parallel sets of steps in cellular defense and development [are] not distinct from one another because they are linked by a protein called p100. ... inflammation leads to an increase in p100, but that p100 is also used in certain steps in development. ... Studies with animals have shown that a little inflammation is necessary for the normal development of the immune system and other organ systems. We discovered that the protein p100 provides the cell with a way in which inflammation can influence development. But there can be too much of a good thing. In the case of chronic inflammation, the presence of too much p100 may overactivate the developmental pathway, resulting in cancer."

Link: http://www.sciencedaily.com/releases/2007/01/070125122719.htm

Following on from the tale of two reviews a couple of days ago, thought I'd point out another article on "How to Live Forever or Die Trying: On the New Immortality." Here, again, is a reviewer reaffirming their belief in the immutability of aging and death with an appeal to those arguments from the gut he finds most appealing:

The reason, for instance, why the human body is fundamentally different to a car is complexity. Each and every cell of the body is millions of times more complex than a car, and we have many billions of cells in our bodies, any one of which can go awry, become a cancer and cause the entire system to collapse in death.

In any case, how many vintage cars are used for everyday city commuting - the sort of hard driving we put our bodies through just by the simple acts of eating and breathing?

Complexity is not a barrier to the possible - it is an indication of the level of work and capabilities of the tools required to undertake the task. Scientists manipulate and investigate fantastically complex systems in the body every day - in essence, the present biotechnology revolution is all about our increasing abilities to understand and use complex systems, which is why it so resembles the computer software and hardware industries in its organization and trajectory. Reaching for complexity as a barrier is akin to saying "it's hard, therefore it's impossible." Nonsense, in other words, meaningless. It's one thing to say, as everyone knows, "we can't repair aging and rejuvenate people today" - but quite another to then dismiss the future precisely because we can't do it today.

Yet in all of his writings, de Grey fails to mention that none of his approaches has failed to extend the lifespan of any organism, let alone humans. In fact, a group of 28 distinguished scientists signed a joint letter in 2005 to one science journal condemning de Grey and the gullible journalists who fall under his spell.

Which is a lie followed by a selectively chosen piece of information, the sign of a reviewer who hasn't actually done any real background reading on the subject of the book. Casting biomedical gerontologist Aubrey de Grey as a crank might be nicely reassuring for someone who wants to hold their world unchanged in concept and boundaries, death, aging and all, but it isn't reality. Sure, we have the 28 conservative gerontologists who signed a joint letter - you'll find disagreement in every field. But how about the 57 signatories of the Scientists' Open Letter on Aging, or the 148 to attend the SENS2 conference organized by de Grey to focus on his view of longevity research, or the many scientists to submit papers to de Grey's journal, the highly-cited Rejuvenation Research, or the staff and leaders of the organizations backing the Longevity Dividend, or the donors and supporters of the Mprize and the Methuselah Foundation, co-founded by de Grey? Just like the actual science itself, none of this is at all hidden from sight ... unless you want to ignore it.

As one of the previously noted reviews said:

Oh yes, very funny. Let’s all have a good laugh at these nutters. That’s how many of us will want to feel. As you read this book, your willingness to laugh will tell you something, namely that you are rather more attached to death than you thought you might be. One becomes defensive when death is challenged. That’s interesting, isn’t it?

Do you believe involuntary suffering and death are good or bad? Do you accept that aging is the greatest cause of involuntary suffering and death? Do you believe that you have a responsibility to help do good in the world? These are simple questions that lead to a simple answer - working to defeat aging is no more a fantasy than working to defeat cancer, and just as great in merit.

Technorati tags: book, life extension, review, SENS

EurekAlert! notes progress towards developing cancer therapies from past years of investigating the p53 gene: "p53 has long been known to play a critical role in the development of many tumors - it is mutated in more than 50 percent of human cancers. Researchers have identified a few compounds that restore p53 function, but until now, it has not been known whether such activity would actually reverse tumor growth in primary tumors. ... In normal cells, p53 controls the cell cycle. ... When p53 is turned off by mutation or deletion, cells are much more likely to become cancerous, because they will divide uncontrollably even when DNA is damaged. ... researchers used engineered mice that had the gene for p53 turned off. But, they also included a genetic 'switch' that allowed the researchers to turn p53 back on after tumors developed. Once the switch was activated, p53 appeared in the tumor cells and the majority of the tumors shrank between 40 and 100 percent. ... The study also revealed that turning on p53 has no damaging effects in normal cells. ... This means you can design drugs that restore p53 and you don't have to worry too much about toxic side effects."

Link: http://www.eurekalert.org/pub_releases/2007-01/miot-mrg012207.php

An interesting and speculative post from Ouroboros: "small body size due to genetic dwarfism and calorie restriction (CR) are both known to extend lifespan in many organisms ... One would therefore expect that animals with DNA repair-related progeroid syndromes would be dissimilar in every regard from dwarf and CR animals - but [results] from a multi-lab collaboration suggest that certain kinds of (life-shortening) DNA repair deficiencies trigger the same alterations in metabolism that are activated during (life-prolonging) CR. ... Short-lived repair mutants seem to divert resources away from growth and into maintenance and repair - because they need more repair. Long-lived dwarf mutants and CR animals divert resources away from growth and into maintenance and repair - because they don't necessarily have (or don't believe they have) enough food to rapidly mature to adulthood. In both cases, we can understand the change in priorities as an attempt to wait out temporarily adverse conditions, waiting for things to change for the better so that the process of maturing to adulthood and sexual maturity can begin again. The DNA repair mutants, sadly, don't know that there's nothing temporary about their adversity."

Link: http://ouroboros.wordpress.com/2007/01/24/how-premature-aging-resembles-calorie-restriction/

Via a couple of posts from Anders Sandberg, my attention was drawn today to an illustration of the scale of medical progress. The latest BMJ contains a list of short essays on important medical milestones since 1840 - glances at small fractions of the enormous progress in medicine that has occurred in the past 167 years.

167 years is not such a long time when you stop to think about it; some people living today have seen two thirds of that span with their own eyes. So much has come to pass; many of the tools of medicine today would have been hard to imagine in the 1950s, let alone the 1840s. Human life expectancy has increased dramatically over this time as the result of improvements in our knowledge and willingness to use it to improve our lot:

Since the Stone Age we have evaluated, interpreted, calculated, and computed. As we observed the effects of our primitive interventions we tried, tried again, and modified our technology. Our legs could take us only so far, until we extended their reach through increasingly sophisticated means of transportation - technology that took us across land and sea and through the air. We overcame the limits of our visual acuity with lenses, opening new vistas of the heavens and the microcosm. Our clinical gaze was augmented by new understandings of anatomy, physiology, and pathology. New tools, such as the stethoscope, radiography, and anaesthesia, let us listen to and see into the human body and tinker with it.

Inevitably, we moved beyond augmenting our limbs and our sense organs. Our powerful brain began to realise its own limitations. With its insatiable urge for self improvement and its unparalleled parallel processing capacity it began building tools to enhance itself. We created external devices that exponentially increased our ability to calculate, analyse, and learn. It took us two millennia to jump from the Babylonian abacus to the mechanical eight digit calculator that Pascal built in the Enlightenment. After only two centuries Charles Babbage envisaged a massive, steam powered mechanical calculator designed to print astronomical tables. Less than a century later Alan Turing created Colossus, an electronic computer that helped end a war plagued by our self destructive drive and power. Over only decades in the second half of the 20th century we developed powerful resources to communicate and exchange unlimited amounts of knowledge, almost anywhere and at any time. We created a global network of computers able to decode the genome; machines capable of seeing our body and its functions in three dimensions; tools to track and control diseases remotely. Computers started to change the way we learn, live, communicate, and heal.

The pace of science, computation and medical engineering is blistering today - why is there any doubt that the medicine of the 2050s will be far more advanced, to the point of extending the present limits of our healthy lives? When we look at what was lacking in 1840 that is known and available in 2007, it seems that those alive then must have lived in the uttermost darkness and suffering. The young of 2050 will see much the same in 2007 - how could people have carried on without reliable cures for cancer, without instant diagnosis of all conditions, without superior, artificial immune systems, without nanomedicine to repair the cellular damage caused by aging?

A look back at history allows us to see the full sweep, power and momentum of medical science, a vision often missed in the day-to-day view of incremental advances. This momentum of progress will carry us into a future of far greater knowledge, capability and longevity - the only questions for we aging individuals are those of pace and timing.

Technorati tags: longevity, medicine

EurekAlert! brings us more on the search for biochemical mechanisms linking learning with a slower progression of Alzheimer's disease: "This study with genetically modified mice is the first to show that short but repeated learning sessions can slow a process known for causing the protein beta amyloid to clump in the brain and form plaques, which disrupt communication between cells and lead to symptoms of Alzheimer's disease. Learning also was found to slow the buildup of hyperphosphorylated-tau, a protein in the brain that can lead to the development of tangles, the other signature lesion of the disease. Scientists say these findings have large implications for the understanding and treatment of Alzheimer's disease, as it is already known that highly educated individuals are less likely to develop the disease than people with less education." Use it or lose it again. What is the machinery of a more active brain doing differently? Insight at the biochemical level may inform the search for more brute-force therapies and preventions.

Link: http://www.eurekalert.org/pub_releases/2007-01/uoc--lsp011807.php

A truth about the engineering mindset from Wired: "Engineers accept that anyone who understands a system also has the power to change it. A real engineer refuses to accept bugs in any code, whether his own, his tools, his operating system or his own body." Biology is information: a mesh of operating systems and programming languages built out of molecules and evolved into a state of complexity. With understanding and tools, control will follow. This is all true. Unfortunately, the author of this article falls into the same old trap of failing to see the difference between the dead end path of pharmacology and basic good health - that will leave us aging and dying in the same way as we are now - and the open path of supporting and encouraging serious research aimed at repairing the damage of aging. It is the latter path of rejuvenation engineering that will lead to radical life extension - healthy, youthful lives of centuries and more. But we won't get there if all that people see is the next drug, the next metabolic tweak to slightly slow the rate of damage. There is a better way forward. Scratch that - there is only one way forward that will not lead all of you reading this now to death by aging, and that is full steam ahead to repair the damage of aging with biotechnology, not slow the rate of damage with metabolic drugs.

Link: http://www.wired.com/news/technology/medtech/1,72518-0.html

I'm pleased to be able to draw your attention to this latest release from the Methuselah Foundation:

The Methuselah Foundation has appointed Allison Taguchi as its Development Officer, responsible for structuring and executing its fundraising efforts. Allison has over 12 years of fundraising and business development experience at research institutes, universities, government agencies, think tanks, and non-governmental organizations. Examples include: Rushford Nanotech Laboratory, Department of Defense, Oakland Military Institute, and University of Hawaii Biotech Research Center.

Working out of the Bay Area, Allison is arranging a series of outreach events throughout 2007 and beyond, at which Dr. Aubrey de Grey, Chairman and Founder of the Foundation, will articulate the SENS (Strategies for Engineered Negligible Senescence) roadmap for directed research into obviating the fundamental mechanisms of aging. Allison said, "I'm looking forward greatly to working with the Methuselah Foundation. We have a slate of SENS-related research projects ready to go that only await funding; these and the Mprize - which will be awarded to researchers who substantially extend the lifespan of laboratory mice - will attract much interest in the Bay Area tech community and beyond."

As you may or may not know, in addition to her past demonstrations of proficiency in the fundraising arena, Taguchi is involved in a number of professional ventures that have grown out of the transhumanist community in past years. These include the Future of Humanity Institute and the Singularity Institute for Artificial Intelligence; Taguchi is quite the hub.

Successful fundraising in any field has a great deal to do with the arcane talent of networking - with the generation and use of a web of connections to better enable the flow of information, reputation and trust. Now that the Methuselah Foundation has now moved into the realm of expecting - and being expected - to raise millions of dollars in research and advocacy funding over the next couple of years, strands in the network are the coin of the realm. Seven-figure donations don't just happen; a great deal of work and energy lies behind each success.

Folk like you and I can continue to help in this process by showing that we care deeply about serious research aimed at the rapid defeat of aging. Doors to the realm of networking and million dollar donations were opened by the actions of hundreds of ordinary people, those who took the initiative to support the Foundation in the years since its creation in 2003. As more of us step forward to demonstrate that we are willing to help eliminate age-related frailty and suffering, more million dollar doors open, and the network of potential wealthy donors grows - and so the faster the scientific community will turn to effectively engage aging.

Success is the greatest predictor for more success - we pebbles are crafting the start of a mighty avalanche, and soon we'll see the huge boulders join in. Let's keep up the good work!

Technorati tags: activism, fundraising, SENS

A growing tumor is successful in its fight to kill the aging body that hosts it by evolving its way into the set of mutations that best help its growth - but what if we could remove the best and most obvious tools from the cancer growth toolkit? Progress in that direction can be found at the Independent: "Doctors often describe cancer as a genetic disease because of the role played by genes in causing the uncontrolled proliferation of a cancerous cell into a tumour. The radical approach is to use molecules of RNA - a substance similar to a gene's DNA - to 'silence' or switch off certain key genes known to be involved in the growth of tumours. One team [has] shown in a laboratory study that it is possible to use large molecules of RNA to switch off a gene responsible for an enzyme called dihydrofolate reductase (DHFR), which is essential for the rapid proliferation of tumour cells. Another team [has] used smaller molecules of RNA in an animal study to switch off a separate gene known to be involved in the rapid growth of brain tumours."

Link: http://news.independent.co.uk/uk/health_medical/article2175040.ece

CCNews notes that researchers at the Buck Institute for Age Research are embarking upon a large screening exercise, searching for new ways to manipulate metabolism to extend longevity: scientists "will screen as many as 120,000 chemical compounds over the next four years to discover which ones impact lifespan in four research models - yeast, nematode worms, fruit flies and mice. ... at the very least we hope to identify 100 chemically distinct compounds that slow aging, opening up new avenues to treat, prevent or postpone age-related conditions ... The largest number of compounds will be screened, in many cases via the use of robotics and other high-tech devices, in the simplest organisms - budding yeast and nematode worms. Chemicals that extend lifespan in those species will go on to be tested in the fruit fly. Chemicals that cause all three species to live longer will be looked at in mice, to see if there is a reversal of the molecular characteristics of aging. The evolutionary distance between yeast and worms predicts that compounds active in both these species are likely to be relevant to mice and humans."

Link: http://www.ccnmag.com/news.php?id=4754

Today, a tale of two book reviews, both of "How to Live Forever or Die Trying: On the New Immortality." But let us look upon them as two knees - for my, how the left knee jerks.

Wake me up in a hundred years:

Bryan Appleyard's How to Live Forever or Die Trying offers an intriguing look at the geeky, freeze-dried, pill-popping world of people who want to go on and on

...

see when he has to swallow his next handful of life-preserving pills. Unruly hair, an uncoordinated body and a wretched dress sense are, of course, the unmistakable indices of intellect, as every senior common room in Oxford testifies. But would you really want to share eternity with freaks like these?

...

Appleyard himself seems unsure. Personal testimony about his childhood dreams and adolescent traumas make clear his dread of death; nevertheless, the experts he interviews are shysters. The immortality they peddle is a specifically American fantasy, the product of a culture infatuated by newness and hostile to the very notion of history.

It seems to me that the right knee, sadly shielded behind the firewall of failing publishing models, has thought things through a little more carefully - diverted further from that grand human tradition of deriving truth from the gut within rather than the much more productive realms of fact and endeavor without.

Death, be not proud:

The title of this book, and the cover, which depicts the Reaper in a bow tie, look like they are trying to make you laugh. This is a book about the possibility of immortality, and, when you pick it up, you imagine fun being poked at mad scientists with their potions and regimes and freezers full of body parts. But it’s not a mocking book, even though, by the end, you might wish it were. This is a serious, frightening, at times brilliant book on immortality. 'Death,' as Appleyard tells us, 'is being attacked on many fronts.'

Most people, when faced with the possibility of immortality, have two immediate thoughts - first, that it’s a good thing, and second, that it’s impossible. Appleyard will make you question both of these convictions. He has spoken to scientists who have studied the science of mortality and found it lacking. They are not mad - or only as mad as, say, Crick and Watson must have sounded, or Heisenberg with his proof that things change when you look at them. Of course, reading about people like this does make you smile sometimes, because challenging death sounds so naive. But soon you will be smiling on the other side of your face.

There is Bruce Klein, of the Immortality Institute, whose aim is 'conquering the blight of involuntary death'. Klein calls death 'the Silent Tsunami'; he explains that 100,000 people die every day, and yet we accept it. His point is that if this was an actual tsunami, people would get their act together. There’s also Ray Kurzweil, who describes nature as 'dramatically suboptimal'. Perhaps most fascinatingly, there is Aubrey de Grey, the long-haired, beer-drinking genius who is applying an engineer’s approach to the problem of death, and whose organisation is called SENS, which stands for 'Strategies for Engineered Negligible Senescence'.

Oh yes, very funny. Let’s all have a good laugh at these nutters. That’s how many of us will want to feel. As you read this book, your willingness to laugh will tell you something, namely that you are rather more attached to death than you thought you might be. One becomes defensive when death is challenged. That’s interesting, isn’t it?

"Immortality" is such an abused word these days, loaded with meanings. Aging, and the frailty and death it brings, are the real targets of the coming biotechnology revolution - understand the human machine and you can repair its worn parts. Why do people defend death by aging and the suffering of billions, or say that aging is impossible to tackle, all the while believing that the biotechnology revolution will soon defeat the complexities of cancer - a similarly challenging problem? It is indeed interesting, the attitudes that exist towards longevity - and a life of years and health - in an era so close to engineering agelessness.

Technorati tags: immortality, life extension

One of the folk working on mitochondrial repair via protofection has said "'The cure for aging' is the instant-death third rail of grantsmanship and we stay away from it." It doesn't matter how relevant your work is to rejuvenation via the slowing or repair of age-related damage, the conservative funding and regulatory culture wants to hear you disclaim any intent in that direction. Sadly, this is only now beginning to slowly change - but where the money is in full flow, this mindset remains well in evidence. Via a Fortune profile piece on Sirtris and the science behind its CR mimetics: "he's determined to avoid any whiff of 'fountain of youth' hype - specifically, of giving the impression that Sirtris is a bunch of flakes chasing miraculous elixirs, which is the kiss of death for a startup trying to raise millions of dollars from hard-nosed money managers. He spends a lot of time explaining that his company is working to cure diseases of aging, not to cure aging itself. There's a difference, especially in the minds of regulators, who view aging as part of the human condition, not an illness warranting treatment." These are the chains of the mind that must be broken if the promise of modern biotechnology can be fulfilled, and our healthy lives greatly lengthened.

Link: http://money.cnn.com/2007/01/18/magazines/fortune/Live_forever.fortune/

The popularity in the press of articles explaining a bonus of an extra year here and a year there to your life span (through some mundane circumstance or lifestyle choice) stands in stark contrast to the comparative unpopularity of articles discussing the serious prospects of engineering additional decades - and then centuries. People are fascinated and eager to read about additional longevity, but at the same time shy away from the very same thing. The frivolous is called from the rooftops, the serious dismissed. It is all very strange; a puzzle waiting to be cracked by those engaged in healthy life extension advocacy. "The average life span for this group was just over 76 years. Winners of the Nobel Prize were found to live 1.4 years longer on average (77.2 years) than those who had 'merely' been nominated for a prize (who lived on average for 75.8 years). When the survey was restricted to only comparing winners and nominees from the same country, the longevity gap widened even more by around another two thirds of a year on average. ... Status seems to work a kind of health-giving magic. Once we do the statistical corrections, walking across that platform in Stockholm apparently adds about 2 years to a scientist's life-span. How status does this, we just don't know."

Link: http://www.sciencedaily.com/releases/2007/01/070116131540.htm

I've been discussing advances in cancer research a fair bit over the past couple of months. Cancer is a big, bad part of the aging process; a haywire form of uncontrolled biochemical rot in the gears of your body. It's waiting for all of us if we manage to engineer the medical technology to evade heart disease, neurodegeneration and all the other failure modes of age-damaged biochemistry that kill before cancer can.

Here is a question for the floor: to what degree is a robust cancer cure sufficient for a future of ongoing, step by step healthy life extension leading to the defeat of death by aging?

What do I mean here? By a robust cancer cure, I mean a foreseeable level of medical technology whereby cancer is neither fatal nor greatly expensive to deal with in the degree to which it occurs in the old today. It can be detected early, eliminated in any but the latest of stages, and doing so will not dramatically increase the patient's expenditures on healthcare. I envisage technology based on microarray scans of blood for the earliest signs of cancer, and targeted, highly efficient therapies capable of eliminating cancer cells without damaging healthy systems in the body - the widespread technology base of 2015 to 2025, give or take a few years, in other words.

By "sufficient" I mean this: if ever more sophisticated refinements on the above themes are all we have to work with, would that be enough to stave off cancer for almost all people if other first generation rejuvenation technologies - in combination with general improvements across the board in medical technology - increased life span by two or three decades?

We envisage healthy life spans to increase in steps; a old person taking advantage of each new step might beat the curve, a little rejuvenation at a time, to live into an age in which aging was truly defeated. The first step, consisting of first generation attempts at most of the repair technologies outlined in biomedical gerontologist Aubrey de Grey's Strategies for Engineered Negligible Senescence (SENS), might plausibly provide a couple of decades of additional healthy life. That would mean a couple of decades in which medical science can further advance and improve - and so on, a step at a time.

The risk of cancer in any tissue increases with age - and as for most failing machines, quite dramatically so in later life. This stems from underlying changes in biochemistry and the simple rules that determine failure rates in machinery based on gradual wear in component parts - possibly the shortening of your telomeres, possibly damage to stem cells, possibly something else, possibly all of the above. Is it good enough to have a good after-the-fact cure on hand when the risk of occurance is increasing enormously with each passing year? Is there a point past which a good therapy is just overloaded by sheer weight of new cancer bursting from your cells, and where does that point occur?

Ultimately, we would want to change our biochemistry so as to prevent cancer from occuring at all. Like all projects aiming to safely re-engineer a very complex system, this will be challenging indeed - but it will get easier with time. At what point will we need to have absolute cancer prevention in hand to beat the curve of aging, and thus remain alive and in good health to take advantage of the next anti-aging technology in line? At what point does a cure for cancer fail us?

Technorati tags: cancer research, life extension

If you are one of the hundreds of millions unfortunate enough to face death by aging prior to the advent of medical technologies capable of rejuvation - of reversing aging by repairing age-related cellular damage - there is still one option remaining to give you a chance at renewed life in the future. This option is cryopreservation: paying a service provider such as Alcor to vitrify your body immediately following clinical death for indefinite low-temperature storage.

Cryonics is the only option for life extension open to many older and seriously ill people: those who cannot wait for the promised therapies of the next few decades. It is the science of placing humans and animals into a low-temperature, biologically unchanging state immediately after clinical death, with the expectation that advances in medical technology may eventually enable full restoration to life and health. A small industry of cryonics providers exists to freeze or vitrify your body on death, in the hopes that future scientists (most likely using nanotechnology and nanomedicine) will be able to revive and repair you.

The practice of cryonics is an ongoing medical experiment with an unknown chance of success. Responsible cryonicists understand that cryonic suspension is an educated gamble. The chances are certainly better than zero, however, and as one wag noted, "the control group in this experiment isn't doing so well." By this, he was referring to the vast number of people who are cremated, buried or otherwise interred. The chances of any plausible future science restoring them is zero. Cryonic suspension is, after all, only the second worst thing that can happen to you.

You are your brain. More precisely, you are a particular arrangement of molecules and fine structures in your brain - structures that are undamaged at small scales by appropriately managed vitrification or freezing. Hurdles remain, however, both in terms of preventing comparatively large-scale fractures, and suitable preparations to reduce cell damage after clinical death but prior to processing for cryopreservation in all cases (including accident). The hurdle of restoring a cryopreserved, fracture-bearing individual to health and life is left to the scientists of the future: it's a challenge, but certainly not one made impossible by the laws of physics. Indeed, we can envisage the classes and capabilities of technology needed quite clearly today, if not the details.

In principle we need only repair the frozen brain, for the brain is the most critical and important structure in the body. Faithfully repairing the liver (or any other secondary tissue) molecule by molecule (or perhaps atom by atom) appears to offer no benefit over simpler techniques -- such as replacement. The calculations and discussions that follow are therefore based on the size and composition of the brain. It should be clear that if repair of the brain is feasible, then the methods employed could (if we wished) be extended in the obvious way to the rest of the body.

The brain, like all the familiar matter in the world around us, is made of atoms. It is the spatial arrangement of these atoms that distinguishes an arm from a leg, the head from the heart, and sickness from health. This view of the brain is the framework for our problem, and it is within this framework that we must work. Our problem, broadly stated, is that the atoms in a frozen brain are in the wrong places. We must put them back where they belong (with perhaps some minor additions and removals, as well as just rearrangements) if we expect to restore the natural functions of this most wonderful organ.

Here's a question: if this level of advanced nanotechnology is required to repair your brain, isn't it fair to assume that building a new body to house your brain is a given at that level of progress? After all, we're not all that far away from being able to cultivate entire replacement organs from stem cells today. If you must undergo cryopreservation, because you were born too soon for the future of rejuvenation medicine, why bring your body along?

The cost of cryopreservation for your head alone is half that of the whole body. Think for a moment: if the objective is to survive to see a future capable of reviving you some number of decades from now, what is more likely to help? Resources - your money - given to preserving your body below the neck, or those same resources dedicated to supporting, growing and otherwise firming up the organization, science and technology base that will be maintaining your storage all those years?

It seems the rational choice to me to preserve your head - your brain - and give the difference to cryonics research and organizational support. Better to make the future revivers expend a little more effort than to fail to do your part to help your cryonics provider (a) carry through to that era and (b) expand their capacity to offer service to more people.

Technorati tag: cryonics

The need for an answer now has a way of bringing people to willfully blind themselves to the realities of uncertainty and risk. This is a familiar sight in that part of the "anti-aging" marketplace that attempts to manipulate common physiological aspects of health by the brute-force application of hormones - pouring fuel on the fire and praying it burns the way you want, in other words. "Roughly 2.4 million prescriptions for testosterone were filled in the U.S. in 2004 -- more than twice the number filled just four years earlier ... the benefits of boosting testosterone levels in otherwise healthy aging men experiencing natural declines in hormone levels are not as well understood. ... Patients and their physicians should be able to make therapeutic decisions with a clear idea of what the risks and benefits are, but in this case that isn't possible. There is still a lot of uncertainty about this treatment ... We have a situation where physicians and patients are essentially in the same boat. Neither is fully informed about testosterone therapy, because the long-term research just hasn't been done."

Link: http://www.webmd.com/content/Article/131/118059.htm?printing=true

Alcor, a cryonics provider, recently posted a helpful overview of the way in which folk of ordinary means fund indefinite low-temperature storage following death, to await future technology capable of repairing the damage of aging and disease. "The following four funding methods are currently accepted by Alcor for new applicants ... 1. Life Insurance.
Used by the vast majority of current Alcor members, this is the most typical funding arrangement because it is affordable on a day-to-day basis. Alcor is designated as both the beneficiary and owner of the life insurance policy (revocable if membership terminated) ... 2. Prepaid - Cash or Equivalent ... 3. Trusts.
All trusts involve some form of fees to the oversight trust company. Some applicants may perceive a potential advantage of trust funding, as it introduces third-party involvement in the trust company, which pays Alcor after the terms of your contract with Alcor have been satisfied. ... 4. Annuity.
An annuity is a 'savings plan with a life insurance company.' Funds are reallocated from other accounts to establish an annuity. An annuity can provide the same level of certainty of funds being available as a life insurance policy."

Link: http://www.alcor.org/BecomeMember/sdfunding.htm

By way of following up on a recently noted article on funding for embryonic stem cell research, here are comments by Ronald Bailey from Reason Magazine: "Instead of being modeled on drug development, perhaps embryonic stem cell research will follow a development path more like that blazed by researchers in assisted reproduction. Rather than being hampered by a paucity of federal research funding perhaps embryonic stem cell research will flourish just as research on assisted reproduction techniques (ART) has. Arguably in vitro fertilization research has proceeded rapidly because of, not in spite of, essentially no federal funding. ... Without intrusive federal oversight and regulation IVF researchers have been able to deploy new techniques such as intracytoplasmic sperm injection, pre-implantation genetic diagnosis, and sperm sorting for sex selection very shortly after they have been developed. Research has stopped in promising areas of ART only when the Feds decide to get involved." It should be no surprise that work is more effective per dollar spent when the funders have a far greater, pressing interest in the outcome, and when there is less regulation to raise costs to no good end.

Link: http://www.reason.com/news/show/118069.html

There is a certain repetition to articles noting the death by aging of the very oldest living humans - you will see them often. Here is one of the latest:

Her nieces and nephews said she loved clothes and loved to travel. They said she was tough, feisty and self-sufficient, but kind. When her parents aged, she took care of them and invited them to live with her in her apartment, the Gazette reported Friday.

When her parents died, she moved to Montreal.

For the past 35 years, she's lived in a nursing home on Gouin Boulevard East.

She earned the distinction as the oldest living woman when 116-year-old Elizabeth Bolden of Tennessee died on Dec. 11, 2006.

Emiliano Mercado del Toro of Puerto Rico is thought to be the world's oldest person. He was born 26 days before Bertrand.

At some point in the near future the oldest person you know, a person already suffering and diminished in capabilities by the ongoing failure of their biochemistry, will die of aging. Then someone else will be the oldest person you know - and he or she will also suffer and die of aging. It will happen again, and again, and again - ever onwards, each life lost just as much a tragedy as the last.

The toll of aging will continue until we choose to develop the medical technology to stop it from continuing. We can do this now. It will take decades, but we can do it, if we can but band together and show the will and the certainty. How many lives - lives close enough to be detailed, valuable, known well and missed deeply - does it take to convince a person of the need to cure aging?

But the king answered in a broken voice: “Yes, we did it, we killed the dragon today. But damn, why did we start so late? This could have been done five, maybe ten years ago! Millions of people wouldn’t have had to die.”

Technorati tags: aging, death

A reminder via EurekAlert! that type 2 diabetes is one age-related disease that you have a lot of control over: "Changing to a healthier lifestyle appears to be at least as effective as taking prescription drugs in reducing the risk of developing Type 2 diabetes ... [Researchers] found that lifestyle changes, e.g. switching to a healthier diet and increasing exercise to be at least as effective as taking prescription drugs. On average, lifestyle changes helped to reduce the risk of developing type 2 diabetes by around half. Lifestyle changes were also less likely to have adverse side-effects. However, the researchers say that both lifestyle changes and prescription drug taking must be sustained in order to prevent the development of Type 2 diabetes." Neglecting basic good health practices has dire consequences on your life span, quality of life and bank account contents. Exercise, eating sensibly, keeping the weight off and dropping bad habits are nothing new - it's not rocket science. Why not make more of an effort to avoid the avoidable and raise your chances of being healthier for longer?

Link: http://www.eurekalert.org/pub_releases/2007-01/bmj-lce011907.php

Here, via OpEdNews.com, is another illustration of the degree to which people see change as a terrible thing, the counterweight when discussing healthy life extension. We hear speakers weighing death and suffering for billions - versus those billions living in good health to see and bring about change - as a choice that requires thought. Amazing; but human psychology is indeed exceptional in ways both good and bad. "It's because of our abbreviated lives that we struggle to fit all the things we want to do, into the little time there is to do them. Bitterness, the acute sense of failure that overtakes so many, results because of nothing more complicated than the repetitious experience of 'That's all. Times up,' as the carny opens the gate on your tilt-a-whirl before you're ready to get off. When science over-runs everything we thought we knew, our Gods, our institutions, all of our notions of governments before and since, even the ethical and moral regards we see as our values, the adjustment humanity will be forced to make will be the most traumatic, but bitter-sweet it has ever suffered." This is just silly and overwrought - people will be people whether they are 20, 80, or hundreds of years old. What "trauma" could possibly match the billion deaths by aging that take place every two decades?

Link: http://www.opednews.com/articles/genera_jon_faul_070114_science__26_ponce_dele.htm

(From the Guardian). An odd and sometimes guarded, inward-looking lot, the folk who want to die much younger than future technology could enable. Sighing about boredom here, about approaching change there - even understanding that a longer life would be a longer span of youth, and that death by aging (left unmentioned) is a horror of frailty and suffering, they'd rather anything but live longer. "It would be like Gilbert's account in Patience of a toffee glut. 'We adore toffee; but toffee for dinner? Toffee for tea? Even toffee would become rather tedious.' ... Eternity would surely pall as readily as toffee." Oblivion is a choice of course, and one we should all be free to make. But this sort of flippancy strikes me as the cloak for twice a value judgement: first of the value they give to being alive, and second upon themselves and their merits as a sentient, living being. If you'd rather suffer and die than change and challenge to live in youth, what does that say about what you're bringing to the table? There is the echo of a fear at the bottom of all this: the fear of being offered working anti-aging medicine, using it, and of embracing life for decades more. If you fear that, what is it you really fear? Change, life, or yourself? Just asking.

Link: http://commentisfree.guardian.co.uk/edward_pearce/2007/01/post_926.html

A couple of recent items circulating through the popular science press illustrate the interesting relationship between cancerous cells and their mitochondria - a relationship that can be exploited to attack cancer. Most of the press has focused on the particular compounds used in the threads of research (dichloroacetate and capsaicin) rather than on the underlying mechanism, which is a pity, and rather indicative of the state of science journalism in general. The hammer is meaningless without the knowledge of how to use it - and a better understanding of the problem may lead one to a more effective tool for the job. Still, one or two articles are actually quite good in their focus on the science:

Cancer cells manage their energy production in a most peculiar way. A healthy cell relies on its mitochondria (descendants of bacteria that took up residence in the single-celled ancestors of animals and plants about 2 billion years ago) to oxidise sugar molecules and release useful energy. Most cancer cells, however, use a less efficient mechanism called glycolysis to power themselves. They thus cut their mitochondria out of the loop.

...

Cancer cells seem to adjust so well to glycolysis that even if blood vessels do grow into a tumour and the oxygen thus returns, they stick with it. From the cancer's point of view that is a very good choice, as one of the other jobs of the mitochondria is to kill a cell if it goes bad - a process known as apoptosis.

The role of dichloroacetate is to re-activate the mitochondria by stimulating an enzyme that feeds pyruvate into their energy-generating cycle. (The drug is already tested and approved for the treatment of certain mitochondrial diseases.) It seems this reactivation also allows the mitochondria to stimulate apoptosis.

So it seems quite feasible to engineer one part of a cancerous cell to kill that cell in a form of biological judo. Some of the best potential therapies for a range of condition these days rely on the use of existing mechanisms, subverted to the task at hand. I imagine there are much more efficient ways of doing this ahead in the future - all part and parcel of the strategy of identifying a biochemical difference in cancer cells and then sending in a therapy that acts on that difference.

But on to the capsaicin and another illustration of the same mechanism, triggered a different way:

The tests on cultures of human lung and pancreatic cancers revealed that the family of molecules to which capsaicin belongs, the vanilloids, bind to proteins in the cancer cell mitochondria causing apoptosis (cell death) without harming surrounding healthy cells.

The Nottingham University breakthrough study raises hopes that the innate vulnerability of all cancers has been discovered and that drugs could now be developed to attack mitochondria in a similar way to capsaicin.

Lead researcher Dr Timothy Bates said that the mitochondria in cancer cells could be targeted by other compounds and that the investigation and development of anti-mitochondrial drugs for cancer chemotherapy was likely to be "extremely significant" in the fight against cancer.

All very interesting; the diversity of cancer research is continually a surprise - it is driving a great deal of new understanding in the functioning of our cells. We will have ever greater need of that knowledge in the years ahead, as scientists continue to work on ways to help us live longer, healthier lives.

Technorati tags: cancer research

From PLoS Biology, a scientist's view of the movement of funds, politics and funding in embryonic stem cell research in the past years: "All this support from states and private donors puts more scientists to work ... With the uncertainty at the federal level [it's] important that the states and private donors are stepping in, 'instead of scientists stepping back and waiting till the policy changes.' ... those hot on the trail of potential cures using stem cells are not about to sit idly by while Washington fiddles. Kerr is hoping for the best in 2007, but he and his California collaborator, Hans Keirstead, are pursuing nonfederal funding 'while we await changes in D. C.' Both are appealing to private philanthropy groups for bridge funding to make sure their work continues. ... Meanwhile the research moves ahead without the centralized control and oversight of the federal government." Can't say I think that last point is a bad thing; expect higher quality and faster progress per dollar spent when research takes place in a much more competitive environment, i.e. when those who hold the purse strings care deeply and personally about results, and misspending has meaningful personal consequences for those who authorize it.

Link: http://dx.doi.org/10.1371/journal.pbio.0050032

An interesting thought from Chris Patil of Ouroboros: "The ability to efficiently scavenge reactive oxygen species such as peroxide makes resveratrol protective against oxidative stress ... Thus the cardioprotective effects of resveratrol (or, if you prefer, the wine in a Mediterranean diet) could be mediated not by the regulatory-biological output of a ligand-receptor interaction but rather by an unassisted chemical reaction between small molecules. ... in order for scientists to make the best choices about how to spend our time, it's important to know how a beneficial molecule is exerting its effects. If it's the receptor-mediated outcome that is most desirable, then we should be working on better ligands: molecules that bind more tightly to the proteins that actually generate the relevant output. On the other hand, if the growing family of salubrious natural products turn out to be valuable primarily for their antioxidant activity, then we should be focusing on generating highly effecting antioxidant compounds that can target every tissue and subcellular structure in the body." On the third hand, it seems to me that both are short-termist, considering the presence of far more promising projects aimed at reversing age-related decline.

Link: http://ouroboros.wordpress.com/2007/01/17/resveratrol-as-an-antioxidant/

Take yourself over to the Center for Responsible Nanotechnology for a good introduction to what is meant by molecular manufacturing. You might read it as "advanced nanotechnology":

Molecular manufacturing is the use of programmable chemistry to build exponential manufacturing systems and high-performance products.

Today's nanotechnology is should be viewed as early nanoscale engineering: it represents the first successful attempts to commercialize and mass-produce products with deliberately designed features of nanoscale lengths. The vision of a mature molecular manufacturing technology base bears much the same relationship to the nanotechnology of today as present day mass-production technology bears to the early innovations in factory technology in the 1800s. In other words: vastly more, better and cheaper techniques taking place in a world of far greater general technological capabilities.

That world is not too far off.

One consequence of mature molecular manufacturing is that, in concept, you can pretty much make anything for the cost of raw materials, a blueprint, and the time it takes to assemble your product. Most items of common usage can be made from raw materials that are essentially free - the component elements of soil and rock. This is a powerful economic liberation - that everything becomes a matter of information: the cost of the blueprint and learning to use the product you just built.

In order to get to this point, we will have had to reach a couple of quite important technological milestones. The first being to build systems that can identify, manage and place trillions of molecules accurately. The second to solve all the problems of computational capacity and complexity management required for the first goal. Once we have that, the sky is the limit; these milestones are important for what they imply about our technological capabiilties outside the realm of molecular manufacturing - such as our ability to understand and control our own biology.

Systems that can identify, manage and place trillions of molecules accurately are not a pipe dream; after all, we are already surrounded by examples. You, for example, are just such a system, albeit somewhat slow at self-assembly to full size. There's nothing in the laws of physics that jumps out and says we can't do this. It's just a matter of time.

If you have the technology base to build a nanoforge to assemble a brick, then you also have the technology base capable of simultaneously assembling and controlling a hundred million medical nanorobots of arbitrary design and programming. Or an artifical lung better than the real thing, or replacements for immune cells that never get old or worn. You get the idea. A brick is just as complex as any portion of the human body if you have to build the thing molecule by molecule; more fault-tolerant, but just as complex.

The open question, while we work away at early healthy life extension technologies like SENS during the next few decades - taking advantage of the biological nanomachines all around us, learning how to better repair, use and engineer them to extend our lives - is how close molecular manufacturing is to reality and then maturity. How long does it take to go from simple nanoforge and a proof-of-principle gram of assembled brick to the understanding needed to build a blood substitute a hundred times better than the old human 1.0 version and invulnerable to disease? What are the steps along the way? What will the business cycles and industries look like?

In the long run, when will we be able to build machinery that does the work of our biological components but is much better and far cheaper? When will we stop adapting and manipulating biology and start building the improved version?

We'd all like to live to find out; should we get there, aging will be something of a moot point, a fault in our biology that can be engineered out should we so choose. All the more reason to work harder on healthy life extension now.

Technorati tags: molecular manufacturing, nanomedicine

A comparatively simple approach to tackling cancer stem cells is reported in Science: "Cancer stem cells are the ultimate source of the tumor, consistently supplying it with new cells. ... Killing these stem cells should allow researchers to hit a tumor where it hurts, yet chemotherapy has proven ineffective as it tends to kill only rapidly dividing cells. ... [researchers] started by comparing cancer stem cells to noncancerous neural stem cells. These neural tissue precursors are concentrated in regions rich in blood vessels. The vessels are lined with endothelial cells, which secrete chemical signals that help stem cell survive. ... after examining over 70 human brain tumors, the researchers found that cancer stem cells were frequently located close to tiny vessels called capillaries. ... Drugs that shrunk the capillaries also caused a significant drop in cancer stem cells and consequently put a damper on tumor growth." Comparatively simple it may be, but this new understanding required the tools of modern biotechnology; as is often the case, greater knowledge leads to better use of older medical technologies.

Link: http://sciencenow.sciencemag.org/cgi/content/full/2007/116/2

If scientists can identify markers for the errant stem cells that create and sustain cancer, then modern biotechnology can build a targeted therapy to destroy those cells. Hence the search for stemness in cancer, and the modest advance noted at Newswise: researchers "took tumor samples from patients undergoing surgery for head and neck squamous cell carcinoma, including cancers of the tongue, larynx, throat and sinus. Cells from the samples were separated based on whether they expressed a marker on their surface called CD44. ... The cells that expressed CD44 were able to grow new tumors, while the cells that did not express CD44 did not grow new tumors. ... This ability to both self-renew and produce different types of cells is a hallmark of stem cells. ... The percent of cells within a tumor expressing CD44 varied from one sample to the next, with one sample composed of as high as 40 percent of these cells. Studies in other cancer types have found the stem cell population to be smaller than 5 percent. ... The CD44-positive cells contain the tumorigenic cells, but we don't think that's a pure population of cancer stem cells. We still need to drill down further to find the subpopulation of those cells that is the pure version."

Link: http://www.newswise.com/articles/view/526585/

I've been pointing out advances at the intersection of cancer and stem cell research in past months; it does look promising, especially now that we're moving into the era of "give me a clear marker on the cell and I can kill it safely with modern biotechnology." A large research infrastructure is presently dedicated to uncovering markers for stem cells as a part of learning how to use them for regenerative therapies - if that is also a path towards the defeat of cancer, so much the better.

It is plausible that our cancers are driven by errant stem cells, and that advancing biotechnology will let us effectively deal with those cells sooner rather than later. Perhaps the most encouraging possibility is that the bulk of cancers, or even increased risk of cancer, might come down to just a small cluster of possible mutations or epimutations:

When the teams compared patterns of gene activity in stem cells from healthy and cancerous tissue they found that those from cancers were often locked in a state in which they carry on multiplying as primitive stem cells, instead of maturing into specific tissues. ... When they're in this state they divide more, and in the process may accumulate additional mutations which ultimately turn them cancerous." From the original paper: "Embryonic stem cells rely on Polycomb group proteins to reversibly repress genes required for differentiation. We report that stem cell Polycomb group targets are up to 12-fold more likely to have cancer-specific promoter DNA hypermethylation than non-targets, supporting a stem cell origin of cancer in which reversible gene repression is replaced by permanent silencing, locking the cell into a perpetual state of self-renewal and thereby predisposing to subsequent malignant transformation.

If cancer results - or even only mostly results - from a single identifiable class of changes in stem cells, there won't be much cancer in the world 20 years from now. We can hope.

However, it is worth airing the skeptical viewpoint - which starts with the observation that next to nothing in the world of biochemistry is as simple as we would like it to be. Cells are hugely complex pieces of machinery, and that complexity is vastly multiplied by the ongoing interactions and lifecycles of trillions of cells in your body. The cancer stem cell skeptic acknowledges the research demonstrating the importance of stem cells to sustaining a cancer, but points out:

• Cancers are characterised by extremely rapid mutation and adaptation as the result of their fast growth and aggressive cell replication
• This is one of the reasons cancers are so hard to treat with more brute force techniques such as radiation and chemotherapy - cancer cell populations very quickly evolve resistance to most of what can (reasonably) safely be tried as a therapy in this arena
• There is no reason per se that this rapid mutation cannot include the mutation of normal cells into stem cells or stem-like states sufficiently empowered to support the cancer
• It is possible that many combinations of a small number of mutations exist to produce cells sufficiently stem-like to support a cancer - and are therefore likely to be created in a rapidly mutating cancer
• Therefore targeting stem cells may or may not be a more effective form of therapy in and of itself - a cancer might just evolve its way into replacing them with one of many different sorts of stem cells or stem-like cells based on new markers and mutations, just as it can evolve resistance to specific toxins

Given the present rate of progress, I think it unlikely that any debate over the effectiveness of identifying and targeting cancer stem cells will remain unsettled past 2012, five years from now. The first therapies based on present day approaches in the laboratory should be somewhere in late trials by that time, and a healthy weight of first results in humans already in hand.

Technorati tags: biotechnology, cancer research

Growth hormone is one of those topics in which the science is fighting a slow and steady uphill battle against the marketing dollars of those making money from the application of growth hormone (or anything that they can pass off as its application). The "anti-aging" industry will make money in the short term, but being on the wrong side of the science is a losing proposition in the long term - they can't waste time and misinform people forever. From the recent past here at Fight Aging!:

Talking About Human Growth Hormone :

Growth hormone, once you cut through the irresponsible marketing, is nothing more than another fairly outmoded workhorse therapy for very specific conditions. The anti-aging marketplace could just as easily have worked itself up into a frothing mania over an osteoporosis drug, or something to mitigate menopausal symptoms - the brand snowballs in size and the money treads science underfoot for these people.

Growth Hormone in the Press Again:

From where I stand, growth hormone therapies appear to be a legitimate old-school style therapy for some age-related and other conditions. As for most old-school medicine, it's a roll of the dice as to whether you'll benefit or suffer - no-one can say for sure what's really going on under the hood, or how your biochemistry will take it. Use is an educated risk assessment that people have to make for themselves - and caveat emptor is a very good rule of thumb when dealing with anything associated with the "anti-aging" marketplace. If you had to stick a pin in the map for anti-aging shyster central, human growth hormone would be it - a pity that the legitimate uses have been buried beneath a cartload of marketing.

Still, in a free society, you could stick whatever you liked into your body provided you were prepared to foot the bill for the consequences. Sadly, we do not live in a free society; insofar as medicine goes, we live in a highly regulated, paternalistic, socialist enclave. A commons has been created, and every potential tragedy leads to calls for further control and expansion rather than the much more sensible abolition of the commons.

In any case, my attention was drawn today to further confirmation of the above viewpoints from the scientific community:

No longevity benefit with growth hormone:

Liu's team undertook a systematic review and analysis of published studies, excluding any that looked at diseases for which growth hormone is an accepted therapy. They focused solely on studies using growth hormone to treat the elderly, specifically those whose main maladies were nothing worse than age and being mildly to moderately overweight. They also included only studies that evaluated the use of the hormone in randomized, controlled clinical trials.

Of all the papers contained in two of the largest databases of medical literature in the world, only 31 met the team's criteria. The 31 studies had a combined total of slightly more than 500 participants, and the average duration of therapy was about six months, said Liu, adding that he was surprised at the limited amount of data in the literature.

"These studies were designed to look at what happens when you give growth hormone to a healthy elderly person," said Liu. "For example, what happens to their bone density, to their exercise levels and to their exercise capacity."

The researchers found that growth hormone had a modest effect on body composition, increasing lean body mass, or muscle, by slightly more than 2 kilograms and decreasing body fat by roughly the same amount.

But, Liu said, "It did not change other clinically important outcomes, such as bone density measurements, cholesterol and lipid measurements, and maximal oxygen consumption." In short, the studies provided no real evidence that the therapy resulted in increased fitness.

"From our review, there's no data to suggest that growth hormone prolongs life, and none of the studies makes that claim," said Liu.

The bottom line is that nothing being sold today - and especially nothing being overhyped today - is going to work spectacular wonders for your longevity. If spectacular longevity is pencilled into your plans for the future, then you're going to have to get up and help make it happen - research and development is needed to make the possible into the real when it comes to healthy life extension, and that requires some degree of support, initiative and effort from all of us.

Technorati tags: anti-aging, growth hormone, longevity

A discussion at Nanowerk reminds us that thinkers have been pondering science and the realm of the possible for healthy life extension for quite some time: "In 1769, Diderot, editor of the Encyclopedie, wrote three whimsical essays known as 'D'Alembert's Dream' recounting imaginary dialogues between himself, his friend d'Alembert, a cultured lady friend, and a physician. ... It seems likely that this century will see Diderot's prescience confirmed. In the coming decades, as pharmacology, artificial intelligence, nanotechnology, and biotechnology converge, life spans will extend well beyond a century. Our senses will extend to perceive sights, sounds and sensations beyond our current abilities. We will remember more of our lives, with greater fidelity. We will master fatigue, arousal and attention, and give ourselves more working intelligence. We will have greater control over our emotions, and be less subject to depression, compulsion and mental illness. ... Even if enhancement therapies aren't cheap, their social benefits will generally make them cost-effective. Diderot bids d'Alembert goodnight by saying 'Give a man, I don't say immortality, but only twice his lifespan, and you'll see what'll happen.'"

Link: http://www.nanowerk.com/news/newsid=1252.php

An impressive demonstration is noted at EurekAlert!: researchers "have successfully used adult stem cells to replace the immune system and bone marrow of mice ... The researchers used multipotent adult progenitor cells (MAPCs), which can be isolated from bone marrow ... Verfaillie and her team isolated MAPCs from mice and expanded them for at least 80 doublings in the lab. They then transplanted the cells into mice that received radiation and thus had no immune system. ... The cells not only survived when transplanted but they completely repopulated the blood system of the mice." Is there a near-term path here towards a viable, safe methodology for replacing an age-damaged and ineffective immune system? Perhaps not, unless another methodology could be used to remove the original system: "Scientists must now understand that mouse MAPCs can make normal blood, and we need to explore how they do it. It is very important to note that MAPCs were not themselves radioprotective, thus they alone could not be used in patients in whom the bone marrow is totally eliminated due to radiation or chemotherapy, but it is still remarkable that they can give rise to blood cells."

Link: http://www.eurekalert.org/pub_releases/2007-01/uom-uom011207.php

Mitochondria are the powerplants of your cells, churning away to turn food into ATP, the common currency of cellular energy. They are also a factor in aging, via the creation of damaging free radicals (such as reactive oxygen species) as a side-effect of their chemical processing. Mitochondrial uncoupling is much as it sounds; a feedback mechanism in which processing is disconnected from ATP production; energy from food goes elsewhere, as heat for example. Because this affects free radical production, it seems to be important in tissue aging: "Faster aging is predicted in more active tissues and animals because of greater reactive oxygen species generation. Yet age-related cell loss is greater in less active cell types, such as type II muscle fibers. Mitochondrial uncoupling has been proposed as a mechanism that reduces reactive oxygen species production and could account for this paradox between longevity and activity. ... These results reject respiration rate as the sole factor impacting the tempo of cellular aging. Instead, they support mild uncoupling as a mechanism protecting mitochondrial function and contributing to the paradoxical longevity of the most active muscle fibers."

Link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=17215370

A common theme at the Longevity Meme is the scientific path towards ever greater, more precise and useful control over our cells - and stem cells in particular, given their importance to cancer, some manifestations of aging and regenerative medicine. Here, EurekAlert! looks at another step forward: "researchers genetically mapped a stem cell gene and its protein product, Laxetin ... This particular gene is important because it helps regulate the number of adult stem cells in the body, particularly in bone marrow. ... The only stem cell population that has been examined for effects of Latexin to date is in bone marrow. ... it is possible, even probable, that other stem cell populations in tissues such as the liver, skin, pancreas or brain may be similarly affected by Latexin. This could open up new therapeutic strategies such as using stem cells for the treatment of other diseases and conditions such as liver disease, diabetes and central nervous system damage as a result of trauma or stroke. ... The findings also will help scientists develop effective methods to modulate stem cell numbers and function for therapeutic uses, and also provide a better understanding of the age-related changes that occur in stem cells."

Link: http://www.eurekalert.org/pub_releases/2007-01/uok-rft011207.php

The day to day operation of living tissue is fantastically complex - not to mention the changes in that operation that stretch out over decades, and the interaction of those changes with lifestyle choices, and the way these changes affect who you are and the medical conditions you suffer. This is one reason that proposed medical research strategies like SENS attempt to find easier paths to cures; paths that do not require a full understanding or extensive manipulation of metabolic processes, the operation of living tissue.

Recent research into the genetics of Alzheimer's disease is illustrative of the complexity of our biology. When looking at medical conditions that result from years or decades of multi-stage, interacting, convoluted changes in biochemistry and cellular behavior, the operation of genes is just another part of the puzzle. It's a highly connected system, which means that knowledge of genes is not a magic map to a cure in most cases; sometimes we get lucky, but Alzheimer's doesn't have that look to it. It's the result of some set of slow failures in functionality that happens to everyone; some folk are unfortunate enough to fail faster due to their genes, or have chosen lifestyles that have much the same effect. But we need Alzheimer's repair and prevention for everyone if we are to take advantage of gains in healthy life span attained through pushing back the onset other common age-related disease.

Alzheimer's gene identified: study

a team of researchers analyzed the faulty processing of the amyloid precursor protein (APP) - long associated with Alzheimer's disease - and linked it to a new gene (SORL1). The five-year study included multiple centres such as Columbia University, Boston University and the Mayo Clinic and tested over 6,000 DNA samples from Caucasians, Hispanics, Israeli-Arabs and African Americans and uncovered two consistent patterns that linked the SORL1 gene to people afflicted with Alzheimer's.

"Instead of scanning all the genes in the entire genome, we had an idea of what an Alzheimer's disease-causing gene would look like based on past discoveries," says senior author University Professor Peter St. George-Hyslop, director of the Centre for Research in Neurodegenerative Diseases (CRND) at the University of Toronto. "We knew that the abnormalities in APP processing and the accumulation of its toxic amyloid beta (Aβ) peptide derivative cause Alzheimer's, so we hypothesized that other genes associated with APP regulation might also cause the disease."

SORL1 governs the distribution of APP inside nerve cells of the brain. When working properly, the SORL1 protein regulates APP by diverting it into specific certain regions of the cell. When the level of the SORL1 gene is reduced, APP accumulates in a different region of the cell, where it is degraded into Aβ fragments - abnormal protein fragments - which then cause Alzheimer's disease.

People At Genetic Risk For Alzheimer's Age Mentally Just Like Noncarriers Until Old Age

The study confirmed that carriers of the APOE4 gene type (allele), which confers higher risk for Alzheimer's, are just like other people their age throughout most of adult life in terms of core mental functions.

...

Performance on all tests (except for reading vocabulary, which tends to hold up with age) declined across age groups, a sign of normal cognitive aging. However, APOE4 did not affect performance at any age. Thus the researchers conclude that at least between ages 20 and 64, people with APOE4 age normally in those central cognitive functions.

This finding suggests that APOE4 heightens the risk for Alzheimer's in old age through an additional, as-yet-unknown process that accelerates or intensifies normal changes, pushing them into the range of disease. Jorm provides an analogy. "In general, hair becomes thinner with age," he says. "However, there are some people who have an additional hereditary factor that makes them bald at an early age."

As a researcher points out in the first paper above, "The recurring theme that genetic causes of Alzheimer's all seem to impact the accumulation of amyloid β-peptide in the brain, and that potential therapies which block Aβ production or toxicity seem to block the disease in animal models, suggests that we're on the right track." That is to say, that research today is predominantly aimed at attempting to understand and manipulate enormously complex metabolic processes in order to effect a change in a known quantity - the buildup of amyloid. Quantifying the usefulness of new findings in this context is a very resource-intensive job; the job is still ongoing for APOE4 after nearly 14 years of work, for example.

There is great value in the knowledge derived from investigating mechanisms. Just as cancer research is yielding a far greater understanding of cellular aging, and AIDS research yields a far greater understanding of viruses and the immune system, Alzheimer's research leads to a greater understanding of biochemistry in the brain. That is a great help to many other areas of medical science - but it isn't necessarily the fastest path to help sufferers. It does make it ever easier to strike off on a faster path, however.

If the buildup of amyloid is indeed the key pathological difference that causes AIzheimers, then efforts to remove it would seem to be the way to go - identify the damage, and repair it, in other words. I place more near-term practical value at this time on work in that direction, such as immunotherapies and vaccines, or efforts to repair the body's natural mechanisms for clearing amyloid. A working strategy to repair Alzheimer's will be a far better tool than therapies aimed at slowing the progression of damage.

Technorati tags: Alzheimer's, medical research

Anne C. recently commented on those folk who object to resources devoted to serious attempts to engineer healthy life extension on the grounds that we should be tackling preventable disease and poverty instead. This is a variation of "equality" viewpoints based around halting progress or tearing down the wealthy - strategies bound to result in poverty for everyone, as they destroy the very engine that creates wealth and technology.

Arguments based on inequality are, at root, made from a misunderstanding - willful or otherwise - of the way in which wealth, medicine and technology are best created. Rapid progress for all requires a free market, strong rule of law and property rights. Such a culture necessarily has a power law distribution of ownership and success. There's a reason the US has led the world in technology, for all that it's going to the dogs nowadays - it's the flip side of the reason that communism, socialism and the politics of envy lead to poverty and suffering.

Creating "equality" by taking from the successful ruins the creation of wealth - very much a non-zero sum game - for all. It takes away the vital incentives and rewards for success. At the end of the process, as demonstrated by all that transpired in the Soviet Union, you are left with the same old inequalities, but now taking place amongst ruins, starvation and disease.

We should embrace inequality in all things that are still expensive enough to require rationing, as it is a natural consequence of the best possible path to creating plenty via rising wealth, falling costs and increasing quality of service and goods. Which is not to say don't help those less fortunate than yourself - just don't set out to help in dumb, counterproductive ways that do little more than make you feel better about yourself. When you advance the edge of progress, the bar of wellbeing is raised for everyone, rich and poor. In any case, Anne had this to say:

Funding longevity research or initiatives like SENS does not mean anyone is ignoring the plight of people in developing nations who lack basic medical care and education. The world is literally teeming with people, many of which have organized to take on the challenges of addressing global suffering -- and though things definitely are not perfect, they are improving in some respects, and I expect that this will continue.

Also, just because people don't announce it publicly every time they make a charitable donation or engage in some sort of endeavor associated with addressing a global threat or crisis, this doesn't mean they aren't doing anything or contributing. I object to the characterization of, say, life-extensionists as people who only care about "the rich". As far as I can tell, all of us who are involved in longevity advocacy care about people, plain and simple. Regardless of age, income, country of origin, ethnic background, you name it.

A person can, and should, maintain awareness of what is going on in the world at large, but this does not mean they can devote all their time and resources to every cause that comes along. If you want to change the world and help people, that doesn't just entail waving your arms around and lamenting what is going wrong, but choosing a few targets and putting some time and energy into them.

Humans may be fairly adept at organizing to get tasks accomplished, but it seems much more likely that more will be accomplished through the parallel efforts of numerous, focused organizations and groups than by everyone trying to get together in one big mass and pick one problem and beat at it until it's gone. The complexity of the world, and the sheer size of the population, makes that a ridiculous prospect.

There is no shame in focusing on a single good cause - there are many people in this world, and many resources lying idle; if you want something done, get up and help do it. You can't do everything, or even just a few things well.

I'm happy to hear challenges to a focus on healthy life extension from those who are working hard on other causes; their devotion is part and parcel of the facets of human nature that get things done and persuade others to the cause. It comes with the territory - you can't throw yourself heart and soul into a task without the conviction that everyone else should be doing exactly the same. There are days on which I'll be saying more or less the same thing right back in return. There is nothing wrong with persuasion.

The undesirables who would be better served by silence are the vocal folk relaxing in their armchairs - or political types ever ready to loudly wield the power of the state to force others to shoulder burdens, but who will never lift a finger nor give a dollar from their own wallets to help out. There's plenty of shame to go around in those quarters.

Technorati tags: activism, life extension

As I've mentioned in the past, scientists are making great strides in applying nanoparticles to therapies requiring the carefully destruction of specific cells - such as cancers. The trick is to use the nanoparticle as a keychain to hold all the biochemical keys, homing devices, sensors, identifiers and therapies needed to get the job done. Over at Nanowerk, you'll find another example of this sort of work, complete with some nice diagrams: researchers "designed nanoparticles they dubbed Probes Encapsulated by Biologically Localized Embedding (PEBBLEs) to carry a variety of agents on their surface, each with a unique function. The particles consist of an iron oxide core that serves as an MRI contrast agent. Attached to them are copies of a cancer-targeting peptide called F3, as well as a light-absorbing compound called photofrin that kills cells when hit with red light. When [researchers] used their PEBBLEs to treat rats previously injected with cancer cells inside their brains they saw very clear results: A single IV injection of a targeted therapeutic nanoparticle dose, coupled with a single 5 min photodynamic therapy treatment, leads not only to an increase in the rat survival rate but accomplishes complete tumor remission."

Link: http://www.nanowerk.com/spotlight/spotid=1240.php

Over at cnews you'll find an article that tries valiantly to make the technologies of the future look like terrible, horrible challenges. This sort of journalistic silliness is far too common. A cure for cancer! Better, more resiliant bodies! No more disease and frailty! Oh no, how will we cope? "Schroeder describes the kind of albatross midnight's children may have to bear. During their lifespan - described as possibly indeterminate by many futurists - this generation could reach what Schroeder calls 'technological maximum' - the peak of technology when humans have exhausted all their potential." More accurately, the point at which this fellow's rather limited imagination can't keep up. The world isn't bounded by what one person can imagine. Thankfully. "We'll still get killed in a car accident, get sick and die, get shot and commit suicide. Death will not go away. What will go away is the assumption that after 70 years, you'll die of natural causes . . . that has huge impacts on society." How horrible, that tens of millions will not be forced to suffer, decay and die each year. What a curse it will be, this promised removal of pain, anguish and millions of deaths. How will we bear it?

Link: http://cnews.canoe.ca/CNEWS/Science/2007/01/02/3134647-sun.html

From Ouroboros, a look at the way in which the relationship between your genes and their effect on your life span is both a little random and a little determined: "[I]n humans only about 25% of the variation in life span can be ascribed to genetic factors to any degree, and even in lab animals where variables can be greatly reduced, only 10-40% of the life span variation has a genetic component. ... Life is like a long dice game, and while starting with a good endowment might let you keep playing for a longer time, eventually everyone craps out, and a run of bad luck can wipe out even the richest starting position rapidly. In between these extremes of genetic predetermination and pure luck, though, a recent paper in Nature Genetics finds another possibility: factors in the organism that are not heritable, yet from an early age can be reasonably good predictors of mortality." It's all very interesting - but you shouldn't forget that the real determination of your healthy life span will be made by the efforts of you and those you band with to support the development of working anti-aging medicine.

Link: http://ouroboros.wordpress.com/2007/01/10/stochastic-effects-in-lifespan-determination/

As noted at Wired - and, more usefully, by Michael Anissimov - this is a noteworthy anniversary for the cryonics community:

January 12th is the day on which the first cryonics patient, Dr. James Bedford, took leave of us. Bedford’s heart stopped beating on Jan. 12, 1967 at the age of 73, and shortly after he became the first person to be cryonically preserved with the intention of future resuscitation. That was 40 years ago. If Bedford were up and kicking today, he’d be 113 years old. In 7 years, his combined pre-suspension and post-suspension age will surpass that of the longest-lived human on record.

Our personality, memories, dreams, and goals have a physical reality - in the connections between neurons in the brain. There is no ambiguity here; the entire field of cognitive science is possible because we know for a fact that the brain is the hardware that runs the software of consciousness. Cryonic suspension preserves that connective map, opening up the possibility that one day it could be reanimated and given new life.

This is true. In modern day science, mind is matter - geography, structure, connections. Collections of molecules in particular places. Vitrify that map at low temperature, and it'll still be there when scientists come to an understanding of how to bring it back to life and mind. Which, from my point of view, is an unpleasant experience to have to go through, and the overall concept has its thorns, but it's a damn sight better than the grave and oblivion.

Just a pity it doesn't have the level of support and understanding it merits. A great pity, and a great waste; a river of lives and minds pouring into the pit with every passing day.

After 40 years, the cryonics community and nascent industry has progressed, but not yet blossomed. I am inclined, at times, to agree with Aubrey de Grey's point of view - that most people will remain unconvinced of the economic rationale (in the broadest sense) for cryonic suspension until real anti-aging medicine or noteworthy progress towards the ability to revive the vitrified has been demonstrated. In other words, when the chance at additional life on the other side of cryopreservation is brought closer in estimate and thus made more valuable in the mind's eye via the magic of time preference.

Technorati tags: cryonics

Early registration is now open for the third Strategies for Engineered Negligible Senescence (SENS) conference: "The purpose of the SENS conference series, like all the SENS initiatives (such as the journal Rejuvenation Research and the Methuselah Mouse Prize), is to expedite the development of truly effective therapies to postpone and treat human aging by tackling it as an engineering problem: not seeking elusive and probably illusory magic bullets, but instead enumerating the accumulating molecular and cellular changes that eventually kill us and identifying ways to repair - reverse - those changes, rather than merely to slow down their further accumulation. Almost 50 illustrious speakers are already confirmed. ... SENS 3 will therefore continue and extend the superlative quality of the first and second SENS conferences, held in 2003 and 2005. The calibre of those meetings can be seen from the abstracts [IABG10, SENS2], the online audio recordings of the talks [IABG10, SENS2] and most of all from the proceedings volumes, which were published as volume 1019 of the prestigious Annals of the New York Academy of Sciences and as issues 9(1) and 9(2) of the high-impact (IF 8.571) journal Rejuvenation Research."

Link: http://www.sens.org/sens3/

Why not a Fight Aging! book? Why not indeed; after all, it would seem I have enough material to pull together (or the head of steam to write even more) for the job, and a point to be made that can be expressed in a paragraph:

We stand within striking distance of the defeat of aging - the defeat of frailty, disease and disability with advancing years. The future of our healthy longevity is up to us. That future depends upon our banding together to provide successful support for the best and most efficient paths forward to real anti-aging, rejuvenation medicine. Oh, and you'll help your own personal chances of living to see this future by some modest amount if you are sensible and proactive about health matters - but the payoff from that effort pales in significance compared to the payoff from your support for research.

Looking back, I have managed to continue to find somewhat novel ways of saying this for something approaching five years now. No signs of letting up yet, as I haven't stumbled upon that magic formulation that will stop the world while everyone listens. But in any case, yes, folks in the online space have pulled together books from less of a start.

But I don't intend to pull together a book.

If a blog post is a short conversation, a book is a big gala presentation; both are essentially one-off short-term events, but it takes a lot of preparation and work to put a book out into the world and make it worth the while. The writing is really the least of it - what makes a book successful is the same thing that makes any gala event successful: networking, marketing, public awareness and reputation. For example, Kurzweil's more recent books have been successful in putting ideas out to the world and into the public conversation not because of the topics, quality of writing, novelty, or any other aspect of the books themselves. They rode on the back of Kurzweil's name recognition, his brand, and the level of marketing that a publisher was willing to invest in that brand - an example of using a reputation to make the points you want to make, writ large upon the broadest stage you can reach. Nothing wrong with that: Kurzweil's return on the investment of his time was large.

In my case, you have to look at what I am trying to achieve: larger and more energetic activist and advocacy communities, primarily, and then more rapid progress towards longer, healthier lives by the most effective methods. It is cost effective for me to write blog posts, provide a news service, put together modest resources for beginners, and cast them all upon the waters to sail in search of an audience. The modern structure of communication tools and culture has made everyone a publisher for fees measured in nickles and dimes, after all. If a post fails to engage anyone and sinks without trace, I have lost little. There will be another tomorrow, and new channels and methods of communication to explore in the next month. It was RSS aggregators back when I started, and it's social news networks now - and it'll be something else next year, helping to make it more cost effective for me to bring people around to my point of view by doing exactly what I am doing here.

But a book - that's a large amount of effort to put on one roll of the dice. Even if I succeeded to the plausible best of my ability, it wouldn't be all that impressive in terms of obtaining the results I value. Another book in a sea of books, nothing to distinguish it from all the others, nothing to bring in the crowds to listen and be persuaded - a mere pebble dropped in the pond, and then gone to the bottom. Don't write a book unless you're already famous somewhere, that's my advice. The rest of us are better off blogging, slow and steady, to build an ongoing persuasive conversation and resource for our cause over time.

Technorati tags: blogging, life extension, writing

ScienCentral looks at recent research into the beneficial effects of calorie restriction on the aging immune system: "when we say caloric restriction we typically mean ... taking about a third fewer calories, or about 30 percent [of] calories, compared to what you would take if you had no dietary restriction at all. And ... not only do animals live longer under this treatment, but also they're much, much healthier. They don't seem to be showing many of the diseases characteristic of old age. ... monkeys on caloric restriction had significantly stronger immune systems. They had more immune cells overall, and, most significantly, had more of a valuable type of immune cell called a naive T cell. Most naive T cells are created early in life. Once they get called into action to fight a specific pathogen, they turn into 'memory T cells' that are only capable of fighting that specific pathogen. But naive T cells are capable of attacking any pathogen, including ones the body has never encountered. ... As we use this naive T cell reserve, we're less and less really prepared to fend off new pathogens."

Link: http://www.sciencentral.com/articles/view.php3?article_id=218392886

Scientists have been looking into telomere length and age-related decline for a number of years now: "The researchers, who measured telomere length in leukocytes, or white blood cells, in 1,500 men aged 45-64 years old, found short telomeres indicate a higher likelihood of developing heart disease. ... Telomeres protect the ends of chromosomes from fraying. They shorten each time a cell divides and the loss is associated with ageing. As telomeres get smaller, the chromosomes can become unstable and at greater risk of mutation. Earlier research had shown that people with heart disease have shorter telomeres but it was not clear until now if telomere length could be a predictive marker for the illness. ... They have shown that it is a predictor. It doesn't say it is functionally linked to heart disease but it is certainly associated with it." The next steps involve a better understanding of how this all fits together - is more pronounced telomere shortening only a symptom of years of stressed and worn biochemistry, or is it sufficiently high in the chain of cause and effect to merit preventative therapies aimed at reducing the progression of age-related decline?

Link: http://news.scotsman.com/latest.cfm?id=60902007

When exercise, mental and physical, improves your condition, this means that a great many changes are taking place in your cells. You are a machine composed of many, many machines; wear and tear in you is built of wear and tear at the level of cells and molecules. "Mice with (a) high spontaneous neurological activity, or subjected to (b) moderate exercise or (c) dietary supplemented with high doses of vitamin E from [showed] an increased survival and a retardation in the development of the neurological deficits associated to aging. During aging there was an increase in dysfunctional brain mitochondria, characterized by an increased content of oxidation products and by a diminished functional activity. ... In brain mitochondria, the activities of enzymes that are critical for mitochondrial function [decreased] progressively during aging. ... increased neurological activity, moderate exercise, and vitamin E supplementation, proved to be effective in increasing mice survival and neurological performances, along with a better mitochondrial function and a lower content of oxidation products." Use it or lose it.

Link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=17127368

Scientists continue to narrow down the biochemical components vital to healthy life extension through calorie restriction (CR). A recent paper (the full PDF is freely available) pins CR effects in yeast down to one gene in the mitochondria: "Deleting the LAT1 gene abolishes life span extension induced by CR. Over-expressing Lat1 extends life span and this life span extension is not further increased by CR. Similar to CR, life span extension by Lat1 over-expression largely requires mitochondrial respiration indicating mitochondrial metabolism plays an important role in CR. Interestingly, Lat1 over-expression does not require the Sir2 family to extend life span, suggesting Lat1 mediates a branch of the CR pathway that functions in parallel to the Sir2 family. ... Our studies suggest that Lat1 over-expression extends life span by increasing metabolic fitness of the cell. CR may therefore also extend life span and ameliorate age-associated diseases by increasing metabolic fitness through regulating central metabolic enzymes." At the present rate of research, I imagine it won't be long before the relevance of this finding to mammals is known.

Link: http://dx.doi.org/10.1074/jbc.M607661200

It looks like matters are gearing up for another round of more intense political battles (or more accurately, battles in which the public at large plays a greater role) over tax dollars for embryonic stem cell research. So much waste - and those folk campaigning in support of tax dollars for research are justifying and propping up the very source of the problem ... the fact that the trough of tax dollars exists at all, alongside politicians with meaningful power and no commensurate accountability for their actions, and for that matter the whole corrupt (and corrupting) system of governance that gives rise to this mess.

If politicians and unelected legislators did not have the power to block, constrain and greatly increase the cost of research and commercialization, this would all be a non-issue. Responsibility for science is far better left to the scientists - in other words the people who have the ideas, raise the funds, do the work, understand what is taking place, and have direct accountability for results.

Anyway.

Here are a couple of items on the dread beast politics that caught my eye while winding my way across the web in search of people performing actual work to advance the science of regenerative medicine - you know, getting out there and doing something, rather than jumping up and down clamoring to spend other people's money for them.

Stem cell research bill resurfaces in Congress:

In the House, voting will proceed on the Stem Cell Research Enhancement Act of 2007, which is identical to the one that was passed in the House and Senate last year and then vetoed by the president. A Senate version of the bipartisan bill should come up for a vote after committee consideration in coming weeks, says Sen. Tom Harkin, D-Iowa, a bill sponsor.

...

Although the House bill is expected to pass easily, the real question is whether it will attract enough votes, two-thirds of the total, to override another veto, says Rep. Diana DeGette, D-Colo., a bill co-sponsor. Last year, the bill passed 235-193. A veto-proof majority is more likely in the Senate, Harkin said Tuesday.

"It is just a matter of time before the bill passes," DeGette says. "Even if it will be the next president of the United States who signs it."

House resumes stem cell research debate:

The author of a study on amniotic stem cells urged Congress on Tuesday not to consider his work a substitute for the search for disease-fighting material from embryonic stem cells.

"Some may be interpreting my research as a substitute for the need to pursue other forms of regenerative medicine therapies, such as those involving embryonic stem cells. I disagree with that assertion," wrote Anthony Atala of Wake Forest University, the author of a study published this week and widely seized upon by opponents of embryonic stem cell research as a more moral option.

And across the pond, yet more of the same nonsense in the UK:

Luddites and Moralists:

Two research teams in London find out today whether they will be allowed to create animal-human hybrid embryos as part of their work. Informally, they have already been told by the Human Fertilisation and Embryology Authority (HFEA) that their application is unlikely to succeed, despite it being allowed under current regulations. Last week several scientists got together to express deep concerns about the impending decision and delivered a stark message: banning the creation of hybrids will stifle development of treatments for diseases such as diabetes and Parkinson's.

...

The only conceivable explanation is that the HFEA is feeling undue political pressure from its host department. The Department of Health seems to have made its decision based on a misconception about public unease over hybrid research. It is difficult not to conclude that the HFEA is worried that funds will be cut off if it doesn't fall into line.

Central control, socialization of cost, arbitrary power over others, lack of accountability for costs of regulation, and willful ignorance of the many times these structures have destroyed cultures in the past - it's the path to a bad place. It's certainly not the path to progress in medical science.

Technorati tags: politics, stem cell research

Chris Patil notes a number of recent papers on progress towards the commercial deployment of sirtuin activators - calorie restriction mimetics, in other words - and ostacles yet in the way: "Given the current regulatory laws in the US and elsewhere, getting drugs approved as anti-aging therapies per se is difficult to say the least, approaching the level of practical impossibility. Beyond the political and sociological challenges of defining aging as a pathology in itself are a huge number of nuts-and-bolts issues: How does one measure successful delays in aging? How does one define a Phase I (or II, or III) population, and secure subject compliance over the relevant timescales? But suppose compounds with anti-aging properties (to be more precise, I should say, 'compounds that target pathways known to modulate lifespan in experimental organisms') are approved for clinical treatment of acute or shorter-term chronic diseases, where the trial populations and standards for efficacy are easier to define. We'd then have anti-aging drugs ready for off-label use after they've been proven effective for their on-label purpose."

Link: http://ouroboros.wordpress.com/2007/01/09/toward-sirtuin-activators-in-the-clinic/

In the past, I've mentioned that you can't expect advancing science to save you from the consequences of negligence - meaning that you have to get up and do something to ensure that your personal future of health and longevity turns out for the best. In the same vein, you can't just sit around and wait for the future of medical science to arrive on schedule, in time. Progress doesn't work that way. The only way technology advances - in medicine, anti-aging science, or any other field of human endeavor - is when folk step up to do the job.

Research and development is hard work: it requires sufficient funding and support to develop the sort of community and infrastructure required to bring new technologies into the world. As I have often mentioned here, the science of repairing the cellular and molecular damage that causes aging is presently lacking such a community and infrastructure. If you would like to see a future in which we do as well as is possible in the healthy longevity stakes, then you'd better jump on in and help out. It isn't going to happen any other way, and we can all contribute to make a difference.

On that note, I'd like to welcome Kevin Dewalt to the growing club of Methuselah Foundation supporters; he has an eminently sensible view of it all:

Ok, I confess that I have an agenda here. My donation to the Methuselah foundation is somewhat selfish. Simply put, I don’t want to die. Since this organization is trying to help me achieve that goal, why wouldn’t I want to donate some resources to help them out?

Let’s think about this from a larger perspective: We are entering an era where it is up to us - you, me, and everyone else who is educated and technically competent enough to be reading this - to turn the world into the place we want it to be.

...

Bottom line: if you don’t like the way the world is, start changing it.

Want to make a difference to the future of aging research and healthy longevity? No-one's stopping you from doing your part: head on over to the Methuselah Foundation and see what you can do to help change the world for the better.

Technorati tags: activism, life extension

Those of us who live to see the world four decades hence will have access to a panoply of impressive medical nanomachinery and biotechnology, as Michael Anissimov points out: "Between 20 and 40 years into the future, we will become capable of building artificial antibodies that outperform their natural equivalents. ... Through their presence and continued operation, they will eliminate all susceptibility to disease in those who have them running through their veins. ... The ultimate upgrade would be [physical] immortality. Everything else pales by comparison. Today, there are already entire movements based around the idea. Realizing the possibility of immortality requires seeing a human being as a physical system - composed of working parts that cooperate to make up the whole, some of which have the tendency to get old and break down. ... Defeating aging, then, would simply require addressing these one by one." We're rubbing sticks together in biotechnology today in comparison to what is known to be possible - but today's work is absolutely necessary if we are to live long enough see the wonders yet to come.

Link: http://www.acceleratingfuture.com/michael/blog/?p=288

(Via EurekAlert!). Medical researchers are demonstrating the construction of ever more complex nanoparticles; as soon as you can safely chain together multiple utility molecules, the sky is the limit. Every new key to metabolism and cellular processes is another tool to add to your latest creation. This is important, because these sorts of modular nanoparticles are looking very promising indeed when it comes to curing cancer. For example, researchers have "developed nanoparticles that seek out tumors and bind to their blood vessels, and then attract more nanoparticles to the tumor target. ... the homing nanoparticle could be used to deliver a 'payload' of an imaging compound, and in the process act as a clotting agent, obstructing as much as 20% of the tumor blood vessels. ... we are now optimizing the process, hoping to obtain a more complete shut-down of blood flow into the tumor to strangle it. We are also in the process of adding a drug delivery function to the particles. These two approaches are synergistic; the more particles we bring into the tumor, the greater the obstruction of the blood flow and more of the drug is delivered into the tumor."

Link: http://www.eurekalert.org/pub_releases/2007-01/bi-hnp010807.php

From Anne C.: "At a meeting yesterday with a group of fellow longevity advocates, one issue that turned into a point of discussion was that of whether it is worth presenting longevity treatments as means to mitigate specific diseases, or whether doing so is simply a distraction from the fundamental issue of addressing aging itself (or whether it really matters). ... Geriatricians are devoted to the alleviation of pain and maintenance of healthy functioning (at least as much as possible) in the face of age-related pathology ... On the other side of things, gerontology is interested in things like root causes and systemic differences between young and old bodies, however, the gerontological approach is more exploratory than action-oriented ... The engineering approach to addressing age-related decline and death is something of a new approach -- one that very well might be the needed 'missing link' between geriatrics and gerontology. An engineering approach is one that focuses on appropriate maintenance of bodily systems, through repair and replacement of worn-out or disease-causing physical elements."

Link: http://rationallongevity.blogspot.com/2007/01/geriatrics-gerontology-and-engineering.html

We're still talking about the SENS fundraising discussion from last Saturday over in this corner of the web. First Anne C.

At a meeting yesterday with a group of fellow longevity advocates, one issue that turned into a point of discussion was that of whether it is worth presenting longevity treatments as means to mitigate specific diseases, or whether doing so is simply a distraction from the fundamental issue of addressing aging itself (or whether it really matters).

Next Mike Linksvayer:

Don't dwell on the more radical implcations of your program (unless they're short term money makers). De Grey claimed that repairing each of the seven causes of aging (with the possible exception of mutant mitochondria) individually would cure a raft of diseases. If true, this should be more than adequate to fund fixes for each of the seven causes individually without ever mentioning any potential for life extension. De Grey claimed this is a hard argument to make, as curing individual diseases through other means will be less expensive than the relevant cause of aging fix. If true, de Grey is either extremely optimistic about conventional medical research or is lying about the level of funding needed for his program, considering the $US billions spent on individual disease research annually. I suspect de Grey is wrong on this point and hope other researchers and organizations take an engineering-fixes-for-causes approach via funding for individual disease research.

As I recall, de Grey said that patching up the pathology of one age-related disease well enough that the patient would die of something else (i.e. let's say push it off for a decade perhaps, or not even that) was cheaper than developing the new technology to repair the root molecular damage. That seems like a fair enough estimate to me, and unfortunately this patch-just-a-little strategy is very much the focus of the mainstream of modern day medical science.

The portion of the discussion touching on fundraising under the banner of defeating aging versus fundraising under the banner of defeating one or more specific age-related diseases (via SENS-like strategies of repairing specific molecular damage) was held a little at cross purposes, I think. Some folk were focused down on critiquing the presentation materials, others on the broader scope of fundraising and influencing the research community, and it wasn't always clear in the moment where comments applied.

In any case, I think I take the opposite side of the argument from Linksvayer above: in my opinion it matters greatly as to the banner you raise funding beneath. The problem we face today is not a lack of funding for medical research per se - rather, it is a culture disinterested in tackling aging head-on. It doesn't matter how much money is flowing into the study of aging or treating age-related disease if the defeat of aging is not a primary, agreed-upon, widely supported goal. There has never been any trouble in raising funding for new methods of tackling specific age-related disease, but look at the rate of progress today in extending healthy life span in the old; it's faster than zero, but if healthy life extension continues to be incidental and inefficient, we will all still age, suffer and die - and not significantly later than we would have done if medical science stood still. In this context here, I rate "not significantly" as a couple of decades - sounds good, but it is enormously worse than what is possible if we get our act together.

It doesn't have to be that way, however - we have a chance to change things quickly enough to matter. The change we need to enact is at the level of infrastructure, understanding and intent. When the expected cost of development and commercialization of new technology runs into the hundreds of billions, it doesn't happen by accident. At that scale, the only change and progress to come about is that enacted deliberately and with intent, in an atmosphere of sufficient support and understanding to make ongoing fundraising and collaboration possible.

In other words, if you're not working on A, don't expect to achieve A.

As I see it, real cultural influence on attitudes towards the defeat of aging can start with breakthroughs in the fundraising process. It starts with respected, successful, wealthy individuals - and later organizations - donating to a cause previously considered fringe. We're seeing the first steps in that process now in the efforts of the Methuselah Foundation: donations from individuals such as Peter Thiel and Paul Glenn send a message to the wider audience precisely because they are explicitly given to help the defeat of aging, as opposed to the defeat of heart disease, or cancer, or any one of the other unpleasant end states caused by aging.

If the people of the world felt the same way about defeating aging as they did about defeating agingcancer, none of us in the healthy life extension community would need to be engaged in this sort of activism and advocacy. There would already be a huge infrastructure dedicated to the problem, and we'd be out there fundraising just like the folk who run for cancer research. This is the context within which Methuselah Foundation fundraising takes place - this is the sea change we need to bring about, by a combination of judicious scientific advances, advocacy, and progress in the fundraising space.

Technorati tags: aging, fundraising, life extension, SENS

Take a look at the Seventh Annual Nanobiotechnology Symposium at the New York Academy of Sciences; this technology base is giving rise to toolsets that will be used to greatly speed research, improve medicine and ultimately lengthen our healthy lifespans. "Microarrays are widely used today in molecular biology to identify and monitor gene expression. ... [researchers] have found a way to produce a surface that results in significantly more reproducible and precise microarray data. Better microarray data [will] lead to better 'genomic snapshots of the genes that are turned on or off' in individuals, potentially allowing doctors to tailor drug treatments to a person's genetic makeup. ... This year he described a tool for predictive pharmacology and toxicology called a 'body on a chip.' Early devices incorporated separate chambers for lung tissue, liver tissue, fat, and other kinds of tissues with a circulation system to emulate blood's transport properties. Although assembling an entire human body on one chip is not the goal, Shuler said, the 'body chips' can be customized - with liver tissue, bone marrow, and two kinds of tumor tissue, for instance - and used to test efficacy and side effects of adjuvant cancer treatments."

Link: http://www.nyas.org/ebriefreps/main.asp?intSubsectionID=4664

An interesting piece of wisdom from the venture capital world stuck in my head yesterday; it's a common trope in every funding environment, in fact, but for some reason I don't recall hearing it expressed quite this way before.

In short: every new idea, every plan, arrives associated with a raft of dumb objections, but you won't convince a smart, educated audience of the merits of your idea by taking time to dispel the dumb objections. The world is full of dumb ideas - many more of them than good ideas. Dumb ideas also arrive accompanied by dumb objections (just look at any average day in politics...), and one of the chores of being involved in a funding organization is to listen to people trying to demonstrate that a dumb idea has merit by demolishing dumb objections to that dumb idea. This is a form of rhetorical alchemy - often performed quite innocently by those sold on a plan that just won't work - that raises red flags for folk in funding organizations. They see all too much of it.

Turning this around to the form I am more familiar with, we have this: when presenting to an experienced source of funding, the factual focus needs to be on (a) demonstrating the merits of your plan, and (b) identifying and demolishing the real, smart objections to it. And of course, communicating the merits of the team who will carry it out the task at hand - which is strictly speaking a part of (a), but it's so vital to talk about the competence, track record and dedication of the people involved in any funding situation that it needs to be made explicit. Ideas are cheap and common - the teams capable of executing on them are rare and consequently worth a great deal.

When it comes to smart plans for the defeat of aging and elimination of age-related frailty, there many, many dumb objections - or at least, things that would be classed as "dumb objection" when you're talking to people who understand the space well and spend their time vetting requests for funding. I've spent a fair amount of time discussing these objections over the past few years, because they are important obstacles to be recognized and surmounted in broader advocacy efforts. I'm talking about things like the Tithonus error, the boredom objection, or the overpopulation objection (and other Malthusian resource arguments) to healthy life extension. For all the wisdom of crowds, people en mass tend to halt and worry at these sorts of non-issues in ways that individuals familiar with the space never do. Wider advocacy or education and setting out to obtain large philanthropic investments from a small community of potential donors are two very separate areas of endeavor - the boulders in the path and the strategies for success are quite different.

Technorati tags: fundraising, life extension

Calorie restriction (CR) blogger and Methuselah Foundation volunteer April Smith is running a short essay contest: "The question inspires perplexitude: why are so many people so hateful (mean, snarky, snotty, pick your word) when they find out that someone, somewhere, eats fewer calories in order to slow his or her biological aging process? We all have our thoughts. Many of you have expressed them eloquently in blog comments. So I've decided to sponsor an essay contest. The prize will be: you get your essay published on the blog." From one of the entries: "When you are afraid, it actually takes courage to recognize your fear and give it its proper name. For some reason, it's more socially acceptable to express anger or even hatred than it is to admit your fears. ... Those of us who have started down the CR path are admitting that we fear death and disease, and we want to do everything in our power to avoid those things as long as possible. We are the fighters. Those who attack us are also afraid of death and disease. But instead of confronting those fears, they reach for anger and hatred - emotions that are apparently easier for them to feel than fear."

Link: http://www.mprize.org/blogs/archives/2007/01/essay_contest_w.html

I've previously mentioned work to extract multipotent stem cells from amniotic fluid: "Scientists have discovered that amniotic fluid is a readily available source of stem cells and have used them to create muscle, bone, fat, blood vessel, nerve and liver cells in the laboratory. ... the newly discovered stem cells, which they have named amniotic fluid-derived stem (AFS) cells, may represent an intermediate stage between embryonic stem cells and adult stem cells. ... The full range of cells that AFS cells can give rise to remains to be determined. So far, we've been successful with every cell type we've attempted to produce from these stem cells. The AFS cells can also produce mature cells that meet tests of function, which suggests their therapeutic value ... functional tests included implanting neural cells created from AFS cells into mice with a degenerative brain disease. The cells grew and 're-populated' the diseased areas. In addition, bone cells produced from the stem cells were successfully used to grow bony tissue in mice, and liver cells were able to secrete urea, which the liver produces from ammonia."

Link: http://www.stemcellresearchnews.com/absolutenm/anmviewer.asp?a=449&z=5

The Daily Yomiuri reports on one more step forward of many: "A team of doctors has succeeded in creating a hepatic cell out of subcutaneous fat, a development that might lead to a regenerative medicine technique that would enable patients with hepatitis or cirrhosis to have their livers repaired. ... the doctors used a cell called mesenchymal stem cell that accounts for about 10 percent of the subcutaneous fat tissue of a human body ... The researchers added three types of proteins that prompt growth to the stem cells, and incubated them for about 40 days. As a result, nearly all cells turned into hepatic cells ... At least 14 types of proteins, including albumin - one of the major components of blood - and drug-metabolizing enzyme, that are known to be synthesized only in the human liver, were detected in the incubated cells ... the researchers injected about 1 million incubated cells into lab mice that were artificially made to develop liver malfunctions. The ammonia level in the mice, which had been rising before injection, dropped to a normal level in one day." Twenty years from now, we'll take it for granted that doctors can treat us with our own cells, transformed to order to suit the particular need.

Link: http://www.yomiuri.co.jp/dy/features/science/20070107TDY01003.htm

I was invited to a modest gathering today; folk had come together to discuss materials and micro-strategy relating to soon-to-commence Methuselah Foundation efforts to raise larger amounts of philanthropic funding for SENS research - research to repair and reverse aging, in other words. Foundation chair Aubrey de Grey presented, and the usual suspects were in attendance to critique content and exchange ideas: a couple of the other Foundation volunteers (including Anne C.), some of the more insightful local venture investors and business owners, general artificial intelligence researchers, a couple of scientists in the medical field, and folk from the Immortality Institute, Singularity Institute and Foresight Institute were in the mix. Very eclectic; quite the interesting crowd.

While the distribution of interests is on my mind, I should say that I've probably mentioned the numerous overlaps between general artificial intelligence, advanced nanotechnology and healthy life extension communities in the past. There are a number of common funding aspirations, funding sources, supporters and advocates - it's very much a shared space in many ways. The growth, fundraising and advocacy challenges faced in these fields are similar enough to make it worth pooling knowledge, resources and networks to make greater progress; this is happening today, and will continue in the years ahead. So many of the people of note move in the same circles now that I can't imagine it going any other way.

In any case; it's no big secret that the Methuselah Foundation has until the end of 2009 to make the best of Peter Thiel's generous pledge of a $3 million matching fund. This means the clock is ticking on raising $6 million for SENS research: the combined sum of $9 million will be enough to fund a range of modest research programs, larger versions of those already underway and funded by the Foundation. That would be a good start, but the Foundation could be in a much better financial state than that three years from now if matters are well managed - expansion can be rapid indeed once you've established your credentials and potential for success. The path to growth is there, it just has to be executed on - this is also no big secret.

Resources for research must come from somewhere if we are to escape our fate of suffering and death by aging. We must explain our goal; educate the public; raise widespread support; motivate the scientific community. We have made good, strong progress in the past few years - but a long road lies ahead. As a community, we have yet to successfully engage and persuade the wealthiest and most conservative of philanthropists, seeking support for modern, aggressive bioengineering approaches to the problem of age-related degeneration.

We can do this. We must do this. Too many lives, too much suffering is at stake to fail.

The meeting today was an early step in bringing Methuselah Foundation fundraising firmly into the big ticket realm: reviewing the raw materials and identifying how to craft a new and effective strategy for the year ahead. What are the best approaches? What resources are needed? Who best to help? What are the well-defined strategies of successful fundraising? How does this all apply to aging and medical research in particular?

As is always the case for early meetings of this nature, it was more of an exercise in raising questions than answering them - suggestions rather than resolutions, feedback on the raw materials rather than the polished result - but it's clear that the process is determinedly underway. It's also clear that a bunch of smart, experienced people are vested in making it work, and the necessary networking and building of connections is taking place energetically behind the scenes. The Methuselah Foundation of a year from now will be a quite different beast from that of today in terms of presentation and focus - a wealthier beast, too, with much more to disburse to longevity research, judging by the potential for progress I saw today.

Do you want to help make this happen? You can, you know. Just make your voice heard.

Technorati tags: activism, life extension, SENS

The New Scientist clearly misses the ball by emphasising difficulty in cell therapy in relation to this research: "When the teams compared patterns of gene activity in stem cells from healthy and cancerous tissue they found that those from cancers were often locked in a state in which they carry on multiplying as primitive stem cells, instead of maturing into specific tissues. ... When they're in this state they divide more, and in the process may accumulate additional mutations which ultimately turn them cancerous." From the original paper: "Embryonic stem cells rely on Polycomb group proteins to reversibly repress genes required for differentiation. We report that stem cell Polycomb group targets are up to 12-fold more likely to have cancer-specific promoter DNA hypermethylation than non-targets, supporting a stem cell origin of cancer in which reversible gene repression is replaced by permanent silencing, locking the cell into a perpetual state of self-renewal and thereby predisposing to subsequent malignant transformation." If cancer stems - or even only mostly stems - from a single class of changes in stem cells, there won't be much cancer in the world 20 years from now.

Link: http://www.newscientist.com/channel/sex/stem-cells/mg19325852.400-cancer-warning-over-stem-cell-therapies.html

(From ScienceDaily). The best advances in science are those that make progress look easy and obvious - always anything but in practice. Simple steps forward in the knowledge and capabilities of biotechnology can often be combined to form tools far more effective than previously existed, as demonstrated here: "bone marrow stem cells stick to adhesive proteins called selectins more strongly than other cells ... selectins grab onto a specific carbohydrate on the surfaces of white blood cells, stem cells, and cancer cells. ... King's group coated a slender plastic tube with selectin. They then did a series of lab experiments, both in vitro and in vivo using rats, with this selectin-coated tube to filter the bloodstream for stem cells. It worked ... Another exciting application of King's invention is filtering the blood for cancer cells ... As a cancer cell flows along the implanted surface, King's device captures it and delivers an apoptosis signal, a biochemical way of telling the cancer cell to kill itself. Within two days, that cancer cell is dead. Normal cells are left totally unharmed because the device selectively targets cancer cells."

Link: http://www.sciencedaily.com/releases/2007/01/070104144824.htm

As Chris Patil of Ouroboros points out, the latest issue of the Journal of Pathology focuses on the pathology of aging - accumulated molecular damage leads to failure of organs and processes, named diseases of aging, and then suffering and death. Against that backdrop, I am pleased to more often see echos of the intent and thinking behind SENS, the Strategies for Engineered Negligible Senescence, out in the scientific community these days. Strong ideas don't exist in a sealed realm; rather they are diffuse at the edges, spreading to cause change. The active efforts of SENS supporters help that process along - and so we can hope to see ever more scientists declaring that something can be done about aging:

The mechanisms of cellular ageing at a genetic, protein and organelle level are becoming clearer, as are some of the more complex associations between environment and ageing. System ageing is also becoming better understood, and the potential biological advantages of ageing are being explored. Many of the advances in these fields are opening up the prospect of targeted therapeutic intervention for ageing and age related disease.

As Chris Patil notes, "The devotion of an entire issue to this subject is just the latest example of the increasing mainstream attention being paid to the biology of aging." There's a lot of good stuff in there, but this caught my eye:

Autophagy, organelles and ageing:

As a result of insufficient digestion of oxidatively damaged macromolecules and organelles by autophagy and other degradative systems, long-lived postmitotic cells, such as cardiac myocytes, neurons and retinal pigment epithelial cells, progressively accumulate biological garbage (waste materials). The latter include lipofuscin (a non-degradable intralysosomal polymeric substance), defective mitochondria and other organelles, and aberrant proteins, often forming aggregates (aggresomes). An interaction between senescent lipofuscin-loaded lysosomes and mitochondria seems to play a pivotal role in the progress of cellular ageing. Lipofuscin deposition hampers autophagic mitochondrial turnover, promoting the accumulation of senescent mitochondria, which are deficient in ATP production but produce increased amounts of reactive oxygen species. Increased oxidative stress, in turn, further enhances damage to both mitochondria and lysosomes, thus diminishing adaptability, triggering mitochondrial and lysosomal pro-apoptotic pathways, and culminating in cell death.

In other words, you need well-functioning lysosomes (the little recycling plants inside your cells that digest failing components and damaging chemicals) to keep your mitochondria (the power plants inside your cells) in good shape. Mitochondria need to be replaced when they are damaged, or else they can start to damage the cell that hosts them - and that damage is a cause of aging. But simply living across the decades generates an ever-increasing load of biochemical junk that lysosomes can't deal with; eventually they become bloated and inefficient.

Long-time readers of this blog will find this an interesting link between past posts on the mitochondrial free radical theory of aging, methods to tackle lipofuscin buildup, and the lysoSENS project - the latter being a search for bacterial enzymes that can degrade and remove this buildup of "biological garbage" in lysosomes and elsewhere in your cells.

The paper above is a good reminder that many classes of age-related cellular damage feed off one another; damage accelerates damage in all failing machinery. This is all the more reason to accelerate the search for ways and means to fix these problems before they kill us!

Technorati tags: aging, gerontology, medical+research

Medical tourism is accelerating, as well it should. Advancing biotechnology, computing power and materials science means that (a) the practice of good medicine is coming down to pretty much the cost of regulation plus the cost of the people running the show, and (b) many more regions of the world have the technology base, medical community and level of economic success to do the job well.

A Filipino doctor has partnered with a Hong Kong-based company to give his countrymen hope in experiencing renewed health and strength with autologous stem cell transplants. There is so much controversy surrounding stem-cell research because of cloning issues but plastic and cosmetic surgeon Dr. Florencio Lucero believes that autologous transplants will not only help Filipinos but also enhance medical tourism in the Philippines. In fact, he said less than a fourth of his over 20 stem cell patients are Filipinos.

This sort of thing is "eat your lunch out from under you" competition for the biotechnology and medical industries of over-regulated US and Europe. Here, competition is relatively muted, squashed beneath the regulatory burden of patents, trials, compliance with a thousand inane laws. Those comparative few who source enough capital make it past the regulatory costs move into the realm of protectionist policies and short term gain - the barrier now behind them is the fence against competition, and it is in their interest to keep that fence high. A high fence means high profits and less of a need to try anything new and better to keep the money coming in.

Let me say this: human beings are damn lazy when there isn't a spear prodding them in the back. It's our nature. Competition is that spear, the serious threat of your profits and edges vanishing elsewhere, forcing you to inventively accomplish more and better for less. Competition is the alchemical weapon that transforms all the worst aspects of human nature into tools to bring progress to all as rapidly and cheaply as possible. The more aggressive, open and unrestricted the competition, the better the resulting service is for the customers - folk like you and I.

So we should all be very pleased to see Asian biotech and medical entrepreneurs eating the very lunch out from underneath late-stage researchers and new businesses in the US and Europe. It's the only way that those insulated folk inside the regulatory fence are going to feel any meaningful pressure to help tear it down - and thus better serve us over the long term.

Technorati tags: competition, economics, medical tourism

Via UCSD News, a look at the way minor age-related damage to blood vessels in the brain adds up over time: "researchers used a laser technique they developed to precisely monitor changes in blood flow resulting from an induced blockage in a tiny artery, or arteriole, in the brains of anesthetized rats. They found that the penetrating arterioles, which connect the blood vessels on the brain's surface with deeper blood vessels, are a vulnerable link in the network. ... This damage is an enormous problem. We think it is part of the dementia picture in Alzheimer's and non-Alzheimer's patients. But until now, we had no insight into the mechanism of the damage, and understanding the mechanism is the first step toward understanding how to prevent it." So the effects of AGE buildup, free radical damage to cholesterol, and other types of age-related molecular damage on blood vessels are more significant in an ongoing fashion than we'd like to think. I hope that as more people learn about the unpleasant facts of aging, more will be motivated to help do something about it.

Link: http://ucsdnews.ucsd.edu/newsrel/science/bottleneck07.asp

You can find the FAQ for the Immortality Institute in the Institute wiki: "How much will it cost to control human aging? Like setting a time frame for curing aging, this is another point at which the best we can do is estimate. Some people set the figure as low as $100 to $300 million, which is less than it takes to develop and bring a new drug to market. Others think it will take $100 billion or more, so as you can see there are a wide spectrum of estimates. Some of the most respected experts in the field put the figure at around $1 billion, but there is likely no way to know for sure. ... Most people who enjoy life can't get enough of it. Even most of those who claim they don't want to live longer than is 'natural' will go to the ends of the earth to cure themselves of cancer, heart disease and injuries when they get stricken. Modern drugs, surgical techniques and diagnostic tools are life extension technologies that few refuse."

Link: http://www.imminst.org/wiki/index.php/FAQ

(From NY1). It should be no new news that public funds are used to buy votes, but it is noteworthy, to me at least, that the battle over directing taxes poured into the trough to embryonic stem cell research has settled this far: "He's calling for a $2 billion state fund for stem cell and other medical research. ... Spitzer's taking the issue directly to the voters, following in the footsteps of California Governor Arnold Schwarzenegger, who sought and got a $3 billion program through a voter referendum. ... If we want to lead healthy lives, live longer, and make sure we can help people, we have to advance science. And stem cell research is one of those branches of medicine that really holds great promise." In other words, ambitious political operators believe that huge public works for stem cell research will buy votes now, regardless of results or follow-through down the line. This would seem to suggest high levels of enthusiasm in the public at large for major advances in the fight against age-related disease (if not for a sane socioeconomic system to live in or the freedom and drive that effective research requires).

Link: http://www.ny1.com/ny1/content/index.jsp?&aid=65614

Interesting news via Bioresearch Online: "NeoStem, a company specializing in adult stem cell collection and banking services for long-term storage for therapeutic uses, has opened the first walk-in, adult stem cell collection and storage center in the US. ... NeoStem provides its patients with adult stem cell collection and banking services via a two step process. The first step is the mobilization, wherein a patient receives injections of a medicine that temporarily allows stem cells to move from a person's bone marrow into the peripheral blood. The second phase is called apheresis, a painless and safe procedure (similar to donating blood) which separates and collects the stem cells from the blood." The open question here is whether this is worth it: what sort of insurance is really provided here? If you believe that the biotechnology revolution will continue unabated, it would seem likely that the medical technicians of 2037 will not need younger frozen cells as an aid to repairing your body. But who can say for sure? At some point the price will be low enough for everyone to hedge their bets at a comfortable cost.

Link: http://www.bioresearchonline.com/content/news/article.asp?DocID=%7B68191C60-7CF8-49E4-AF39-B27B660845D8%7D

This is the age of barnstorming and invention in biotechnology - an age wherein one can speculate about much more complex variations of inserting tab A into slot B without too much fear of proposing an impossibility. Thinking in that vein, I should mention an article I noticed on the topic of bacteria that feed upon mitochondria:

"We'd never seen anything like this before," Lo says, as he opens the image files on his laptop on a rainy afternoon in Sydney. "They seem to get in between the inner and outer mitochondrial membranes and eat the mitochondria up. In the end you've just got this empty sack."

"It's a very novel observation," says Scott O'Neill, a specialist in invertebrate endosymbionts and head of the School of Integrative Science at the University of Queensland, who wasn't involved in the research. O'Neill, whose recent work has focused on the bacterium Wolbachia, says he wasn't aware of any other bacteria that live inside mitochondria. "It's pretty surprising to see a bacterial species living inside the mitochondrion, which itself was a bacterium," he says. "I think it is significant." Bill Ballard, a mitochondrial specialist from the University of New South Wales, agrees. "This is, as far as I know, the first [bacterium] that actually infects within the mitochondria," he says. "It's a pretty cool paper."

Lo's newly found organism doesn't seem to have any negative effects on the ticks. "About half the mitochondria don't get infected," he says, "so perhaps they are only destroying old ones. We don't really know what's going on."

Perhaps distracted by the Star Wars references, I didn't stop to link this to our mammalian problem of accumulating mitochondrial damage - one of the roots of age-related degeneration and disease. Damaged mitochondria take over a fraction of your cells over the decades, turning them into mass exporters of damaging free radicals into the body at large. A regular at the Immortality Institute forums did sit up and take notice, however:

So I'm wondering if these hungry bacteria (mito-phages?) could be reprogrammed to kill defective mitochondria in particular.

Considering all the other things that bacteria have been engineered into doing for us to date, it doesn't seem outside the realm of the possible - although it could certainly be in the realm of "too hard and expensive this decade or next." After all, there has to be some identifiable biochemical methodology already present for our cell to recognize damaged mitochondria - how would one engineer a bacteria to do as much, or to otherwise prefer consuming the damaged mitochondria that lead to aging?

More practical and immediate methods of dealing with damaged mitochondria appear to be in the pipeline - such as protofection - but that's no reason to refrain from speculating on novel or more distant approaches. The more the merrier.

Technorati tags: aging, biotechnology, science

Remember the dead, felled by aging - and those still dying. For in their suffering, they have still made the effort to help you live a longer, healthier life than theirs: "I do about 100 public talks a year and I ask them, as I would ask you - 'Consider being in our brain bank. Consider giving us your brain after you die for our research in Alzheimer's and Parkinson's and these other age-related disorders,' and people have done that in droves. ... In 2005, SHRI expanded its brain bank to include body donations as Dr. Rogers and the other researchers at the institute began realizing the advantages the institute has for studying Alzheimer's and Parkinson's disease would apply to every other age-related disorder. Another deciding factor was people donating their brains began asking the institute to also take their entire bodies. Of the 1,000-plus people in SHRI's brain bank, nearly 70-80 percent now have signed up to donate the rest of their bodies upon death." What have you done recently to help bring on the future of therapies for age-related conditions?

Link: http://www.newszap.com/articles/2007/01/02/az/west_valley/sc04.txt

If dendrimers are the sharp end of nanoscale engineering in cancer research, you'll find there's plenty still going on further back up the nanotechnology wedge. From the MIT Technology Review: "One of these new approaches places gold-coated nanoparticles, called nanoshells, inside tumors and then heats them with infrared light until the cancer cells die. ... These spheres are small enough (about 100 nanometers in diameter) to slip through gaps in blood vessels that feed tumors. So as they circulate in the bloodstream, they gradually accumulate at tumor sites. ... We shine light through the skin, and in just a few minutes, the tumor is heated up. In the studies that were initially reported - and this has been repeated now more than 20 times in at least three different animal models - we have seen essentially 100 percent tumor remission." Cancer is one of the big bugbears of aging - the sooner scientists become very good at killing it, the better.

Link: http://www.technologyreview.com/printer_friendly_article.aspx?id=17956

I look at a great deal of the popular press on aging and see articles informed by the strange, deep-seated belief that nothing will change - that the only action of merit is rearranging or understanding the minutiae. In a world in which we are quite possibly a couple of decades away from adding those couple of decades back on to healthy life spans, articles that treat a year of difference in life expectancy for one racial group over another as an issue of vital importance seem to drift in from some different, dream-ridden reality.

For example, a recent analysis by Irma T. Elo, a demographer at the University of Pennsylvania, indicates that a 65-year-old white woman will live, on average, an additional 18.9 years. But a 65-year-old Hispanic woman who immigrated to the United States will live an additional 19.8 years, a significant difference.

The longevity difference persists even though Hispanic immigrants tend to be like Mrs. Lara, poor and poorly educated and lacking health care. It persists even though, like Mrs. Lara, they get chronic diseases like arthritis and high blood pressure and are often overweight.

“Everyone,” said Kyriakos S. Markides, who directs the Division of Sociomedical Sciences at the University of Texas in Galveston, “is trying to figure out what the hell is going on.”

It's not a reality I'd like to live in - one of a narrow fascination with the color of pebbles at the site of construction of a mighty dam. The pebbles will be there tomorrow, and tens of millions are dying of aging now. Yet pebbles it is, a focus here on researchers who turn the tools of modern science to trivial pursuits in the face of an ongoing avalanche of death and suffering. We could be doing far more to halt the death and suffer of aging - but not a word here on those working to make a difference.

This next article isn't much better:

“The idea was, when a state changed compulsory schooling from, say, six years to seven years, would the people who were forced to go to school for six years live as long as the people the next year who had to go for seven years,” Dr. Lleras-Muney asked.

All she would have to do was to go back and find the laws in the different states and then use data from the census to find out how long people lived before and after the law in each state was changed.

“I was very excited for about three seconds,” she says. Then she realized how onerous it could be to comb through the state archives.

But when her analysis was finished, Dr. Lleras-Muney says, “I was surprised, I was really surprised.” It turned out that life expectancy at age 35 was extended by as much as one and a half years simply by going to school for one extra year.

So much effort going into filling in the dots, to picking at the grains of what is, and narry a mention of what could be done today (not to mention what is being done today) to work towards a real difference - not a year for a few, but decades for all. What a hole we have dug for ourselves in our present culture and its attitudes towards aging, towards change! The passive life is little better than death, and the popular press is ever the mirror held up to a passive life; the rejection of change; the numbing of the mind to the new; the discarding of individual responsibility for a better future.

So it's deckchairs on the titanic, from here until your allotted part is spent. Hah! I would hope that we can all sense there is more than that to a life well-lived. What of building, what of creating the new? We humans can change the rules of the game - and here in modern biotechnology we have the chance to change some of the oldest rules of all, to bring about the defeat of aging, an end to suffering, frailty and death for billions in the decades ahead.

Technorati tags: aging, life extension, media

The sensible practice of calorie restriction (CR) - for health and the aim of greater healthy longevity - tends to inspire some merged set of knee-jerk responses drawn from (a) the pool of poorly thought-out objections to enhanced longevity, and (b) the motley collection of ridiculous objections to healthy eating. Human beings - smart creatures, but basically built out of ape - are very normalized; so long as everyone is doing it, any damaging behavior will have its legion of defenders and justifications pulled from thin air. Not to mention the fake array of moral judgements; you'll find every variety of condemnation in the sordid history of "you're not the same as us." It is a pity that we humans haven't moved past that point yet.

So - smoking, empire-building, and so forth; these are norms, and so too with eating more than is good for you in the long term - which is to say, eating ad libitum. Veer from the norm on a better path, and you'll soon be hearing the squawks of outrage. April Smith recently gave a good response to one set of complaints regarding the practice of CR:

Third, you write:

"As far as I can tell, none of these people have children, and they all are fairly well off."

As a union organizer, I am very sensitive to the class implications of most everything. ... I find that my food budget is actually less now than it was before I started CR because while I still enjoy the occasional meal out at one of our fabulous Philly restaurants, I eat out much less, and I never grab fast food takeout. By packing my food for work (often both lunch and dinner, as I work a whole lot of 12 and 16 hour days) and enjoying homecooked meals with my partner, I save a whole lot of money.

...

If we are to conquer the obesity epidemic that is robbing the majority of our citizens of their health, we need to develop attitudes towards food that don't involve moral judgement.

I find class judgements heaped upon people who are making the effort to better manage their health equally annoying, though possibly for different reasons. It is sheer laziness, self-protective delusion, that leads a person to build a construct around skin color, health, lifestyle choices - and then extend it to the alleged cost of goods. It is a vindictive, unpleasant view of the world, as are most such viewpoints when allowed to thrive independent of any factual input.

Ignore people who exhibit a disdain for facts as guidance; they won't know what they're talking about. Instead learn how to productively listen to what the scientists have to say when it comes to health and longevity. You'll do well by that choice.

Technorati tags: calorie restriction, health

(From ScienceDaily). Cancers are biochemically very varied; this means the defeat of one specific type of cancer is often of little direct use against others. But discovering common mechanisms across many types of cancer greatly simplifies the problem. Here, a new study "identifies a specific enzyme that can cause the death of cancer cells. Researchers studied the behavior of an enzyme called sphingosine phosphate lyase (SPL), which can regulate cell growth and death by lowering the levels of a natural, growth-promoting lipid called sphingosine-1-phosphate, or S1P. ... The enzyme SPL senses when a cell has sustained damage or is undergoing mutations. Once the enzyme is aware of these changes it responds by killing the cell. We hope to find new ways to leverage the body's own natural responses to these mutated or damaged cells to target cancer cells. ... Although we're beginning our studies in colon cancer, we believe our research findings will have a direct impact on investigations for other cancers."

Link: http://www.sciencedaily.com/releases/2006/11/061120182022.htm

As the necessary techniques and technologies for the use of stem cells spread and reduce in cost, specialists in all sorts of fields experiment more readily with regenerative medicine. An example can be found at Medical News Today: "Every 30 minutes a diabetic patient loses the use of his bottom limb due to the ulceration of tissues that degenerates into a necrosis, which is a typical side effect of this disease. ... We employed a murine model that can develop ulcers similar to those observed in humans. Then we administered a specific subpopulation of [vascular progenitor cells] VPCs and, a week after the treatment, we checked what was the overall effect on the ulcers. We observed that the treated lesions had become thinner and smaller compared to the untreated ones, and that they were surrounded by a number of newborn capillaries, indicating that a regeneration process was ongoing ... scientists noticed that VPCs stimulated cellular proliferation and inhibited cellular apoptosis, a defensive mechanism which is active also in necrotic tissues that the organism resorts to when it is unable to heal damages."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=59712